Note: Descriptions are shown in the official language in which they were submitted.
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
ENRICHED ALCOHOLIC BEVERAGES
FIELD OF THE INVENTION
The present invention, in some embodiments thereof, relates to alcoholic
products,
more specifically, but not exclusively to enriched alcoholic beverages.
BACKGROUND
The element which accounts for the psychotropic effect caused by alcoholic
beverages is ethanol, a two-carbon chain alcohol molecule that interacts with
neurotransmitter systems in the brain, and directly affects brain chemistry by
altering the
levels of some neurotransmitters. Ethanol has dual properties both of a
stimulant and a
depressant since it affects both "excitatory" neurotransmitters and
"inhibitory" neurotransmitters. As a depressant, it reduces energy levels, and
slows down
thought, speech and movements, exerts relaxation and drowsiness, mainly by
increasing
production of the inhibitory neurotransmitter GABA, and suppressing the
excitatory
neurotransmitter glutamate.
As a stimulant, ethanol indirectly causes release of dopamine in the reward
pathway
in the nucleus accumbens (NAc) part of the brain, which accounts for euphoric
feeling,
cheerful mood and incentive to seek pleasure. Dopamine is released to the
synapse upon
alcohol consumption, and the more dopamine is released the merrier and joyful
a person
becomes. Re-uptake of dopamine which follows and, thereby, decreased levels of
the
neurotransmitter in the synapse, leads to a down feelings and depression which
often
characterize alcohol withdrawal or sobering up.
Excessive and/or prolonged alcohol consumption may have some undesired short-
term physiological and psychological effects such as gastric irritation,
anxiety disorders
and other excitable states, and highly undesired longer-term effects such as
cirrhosis,
cardiomyopathy and dementia. Alcohol consumption may lead to intoxication,
which, in
turn, can have serious consequences such as accidents and uncontrolled violent
behavior
with subsequent medical complications.
1
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
The standard way alcohol is consumed is by drinking, usually over a few hours.
In
the case of beers/lagers, alcohol (i.e., ethanol) is provided as relatively
dilute solution,
wines are stronger, and spirits contain the maximum alcohol concentration.
One approach to reduce or abolish the undesired effects of ethanol is to
reduce the
concentration of alcohol in drinks. Dealcoholized beverages have been known
for nearly
100 years, and are disclosed, for example, in U.S. Patent Nos. 1,390,710,
1,256,894,
6,472,009, 1,401,700, 4,999,209, and 4,612,916. While removing alcohol may
seem a
practical option for beers, in some cases, especially in wine and spirits,
there is a marked
deterioration in taste, bouquet, and other qualities of the beverage due to
processes
performed to eliminate or reduce alcohol content, such as boiling or steaming.
Another approach which has been practiced is the safer alcohol approach, which
utilizes drugs that act in a similar way to alcohol but are free of some of
its immediate
adverse effects, such as gastric irritation, and do not produce the longer-
term effects such
as cirrhosis, cardiomyopathy and dementia. However, all the drugs had limited
use due to
development of dependence thereon, and/or abuse thereof.
There is an unmet need for "safer" consumption of alcoholic beverages that
would
not deprive the drinker from the pleasure and psychotropic and psychoactive
effects
provided by drinking alcohol, yet, would reduce or even be devoid of the
adverse effects
associated with alcohol consumption, particularly with intoxication.
SUMMARY
In an aspect of the present disclosure, an alcoholic food product is provided
comprising an edible base material, which may be a liquid, solid or semi-solid
edible
substance, for example, liquid, alcohol, and at least one neurotransmitter
and/or at least one
neurotransmitter precursor. The food product thus provided is an alcoholic
food product,
namely a food product that essentially contains a certain amount of alcohol
for example,
from about 0.5% to about 98% by volume or by weight. The inclusion of a
neurotransmitter
and/or a precursor thereof in the alcoholic food product, enriches the
alcoholic food product
with certain qualities which impart it the ability to effect certain desired
psychotropic and
psychoactive effects upon consumption thereof.
In some embodiments, a disclosed enriched alcoholic food product is an
enriched
alcoholic beverage such as beer, wine, spirit, cider, perry and alcopop.
2
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
The neurotransmitter may be, for example, norepinephrine, epinephrine,
serotonin,
dopamine, endorphin, acetylcholine, gamma-aminobutyric acid (GABA), and any
combination thereof. The neurotransmitter precursor may be, for example, a
norepinephrine precursor, for example dopamine; an epinephrine precursor; a
serotonin
precursor, for example, 5-hydroxytriptophan; a dopamine precursor such as L-
phanylalanina, L-tyrosine or levodopa; an endorphin precursor; an
acetylcholine precursor;
or a gamma-aminobutyric acid (GABA) precursor, and any combination thereof.
In exemplary embodiments, a disclosed enriched alcoholic beverage comprises
the
dopamine precursor tyrosine, in amounts ranging, e.g., from about 10 mg to
about 5000
mg per 1 liter, for example, from about 100 mg/L to about 1000 mg/L.
A contemplated enriched alcoholic food product, for example, enriched
alcoholic
beverage, may further comprise one or more psychostimulant substances, namely,
a
substance that is directly or indirectly involved in enhancement of a
neurotransmitter
synthesis and/or stability, inhibition of degradation of a neurotransmitter
and/or inhibition
of reuptake of a neurotransmitter. Such a psychostimulant is exemplified in
some
embodiments, by caffeine, wherein the amount of caffeine in a disclosed
enriched alcoholic
food product may be from about 10 mg/L to about 750 mg/L.
In exemplary embodiments, an enriched beer is provided, comprising tyrosine
and
caffeine, for example, ale, stout, porter, or lager.
The alcoholic food product and/or the enriched alcoholic beverage, upon
consumption thereof, exerts one or more positive psychoactive effects and/or
one or more
positive psychotropic effects which may commence 5 minutes and last up to 24
hours, or
even up to 48 hours after alcohol consumption. For example, consumption of a
disclosed
enriched alcoholic beverage such as beer may promote enhanced and prolonged
sense of
euphoria.
A contemplated enriched beer, wine, spirit, alcopop and/or cider provided
herein
may exert upon a consumer stimulant effects such as elevated mood (high
spirit), energy,
excitement, talkativeness, vigorous and vitality which exceed in intensity and
duration of
similar effects exerted by a corresponding non-enriched beer, wine, spirit,
alcopop or cider,
while reducing intoxication effects and sedative effects such as difficulty in
concentrating,
3
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
down feeling, heavy head, heavy body, sedative, slow thinking, and
sluggishness compared
to corresponding non-enriched alcoholic beverages.
Also provided herein is a process for the preparation of an enriched alcoholic
beverage, such as beer, wine, whisky, vodka a liquor, comprising combining a
base
alcoholic liquid with one or more neurotransmitter precursors, and,
optionally, one or more
psychostimulant substances.
Unless otherwise defined, all technical and/or scientific terms used herein
have the
same meaning as commonly understood by one of ordinary skill in the art to
which the
invention pertains. Although methods and materials similar or equivalent to
those described
herein can be used in the practice or testing of embodiments of the invention,
exemplary
methods and/or materials are described below. In case of conflict, the patent
specification,
including definitions, will control. In addition, the materials, methods, and
examples are
illustrative only and are not intended to be necessarily limiting.
BRIEF DESCRIPTION OF THE FIGURES
[0001] Some embodiments of the invention are herein described, by way of
example only,
with reference to the accompanying drawings. With specific reference now to
the drawings
in detail, it is stressed that the particulars shown are by way of example and
for purposes
of illustrative discussion of embodiments of the invention. In this regard,
the description
taken with the drawings makes apparent to those skilled in the art how
embodiments of the
invention may be practiced.
[0002] In the drawings:
Figs. 1A-1B are bar graphs showing STIM (short for "stimulant effects") values
obtained in an exemplary Biphasic Alcohol Effects Scale (BAES) test conducted
with
enriched beer of the disclosure (1B) and a corresponding non-enriched beer
(1A); and
Figs. 2A-2B are bar graphs showing SED (short for "sedative effects") values
obtained in an exemplary Biphasic Alcohol Effects Scale (BAES) test conducted
with
enriched beer of the disclosure (1B) and a corresponding non-enriched beer
(1A).
4
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
DETAILED DESCRIPTION
The present invention, in some embodiments thereof, relates to enriched
alcoholic
food products, more specifically, but not exclusively to enriched alcoholic
beverages.
Alcohol is one of the favorite, commonly used, yet a somehow dangerous
psychoactive substance. The prevailing and predominant way alcohol is consumed
is by
drinking alcoholic beverages, usually over a few hours. People consume alcohol
for several
reasons such as quenching thirst, heating or cooling the drinker, for the
taste of alcohol, the
association alcoholic beverages have with other aspects of life such as food
and friendship,
and mostly due to the psychological and psychotropic effects of alcohol
associated with
alcohol consumption. Consuming alcohol often confers upon the consumer a
euphoric
feeling, a cheerful mood, relaxation, and a reduced self-awareness. Part of
the pleasure of
alcohol - at least for the non-dependent consumer - is the taste and the
associated rituals of
consumption that may fill primitive appetitive functions.
While seeking for the emotional and psychological benefits when consuming
alcoholic products, there are, inherently, short term and long-term undesired
consequences
of consuming alcohol, more so when consuming excessive amount of alcohol.
Dealcoholized beverages, such as beer and wine, designed in attempt to address
the
need to reduce the hazardous consequences of alcohol intoxication, are
available in
reasonably palatable forms. However, while non-alcoholic drinks can fill such
use-values
of alcoholic beverages as quenching thirst and heating or cooling the drinker,
they do not
provide the range of psychoactivity and palatability which people are seeking
in alcohol.
Unless stated otherwise, "alcohol" as referred to herein is ethanol.
The present disclosure is based on a discovery by the present inventor that
the
effects associated with consumption of alcoholic food products, for example,
alcoholic
beverages, that contain a neurotransmitter precursor, particularly the
pleasurable effects,
may be enhanced and prolonged without the need to increase the amount of
alcohol in the
product. Moreover, the present inventor envisaged and successfully obtained
alcoholic
beverages containing at least one neurotransmitter and/or a precursor thereof,
and
optionally further containing a psychostimulant substances such as caffeine,
which provide
to the consumer stronger and continuing euphoric feeling while minimizing and
even
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
circumventing at least some of the non-pleasurable effects associated with
alcohol
consumption, particularly the undesired physical and emotional sensations of
intoxication.
Disclosed herein is a discovery by the present inventor that consumption of
alcoholic food products containing neurotransmitter precursors affects the
level of certain
neurotransmitters in the brain, for example neurotransmitters that are boosted
or released
due to alcohol consumption. Alteration, for example, elevation, of certain
brain
neurotransmitters level, increases or enhances, e.g., the euphoric sensation
provided or
bestowed by alcohol. This euphoric feeling lasts longer than that induced by
consuming
alcohol alone, and, furthermore, it is mostly not accompanied by undesired
physiological
and psychological short-term effects associated with the concomitant and
rather intense
decrease in neurotransmitters level that follows shortly afterward.
In an aspect of the disclosure, there is provided a food product comprising an
edible
base material, alcohol and one or more neurotransmitters and/or
neurotransmitter
precursors.
The term "food product" as used herein refers to a substance that can be used
or
prepared for use as food by humans or non-humans.
"Alcoholic food product" (or "alcoholic product") is a composition of an
edible
base material defined herein as any substance composed of carbohydrates, fats,
proteins
and/or water, and alcohol (e.g., ethanol) in the amount of 0-99%, for example
from about
1% to about 20%, from about 1% to about 5%, from about 3% to about 8%, from
about
5% to about 10%, from about 8% to about 12%, from about 10% to about 15%, from
about
15% to about 25%, from about 20% to about 30%, from about 25% to about 40%,
from
about 30% to about 50%, from about 40% to about 60%, from about 50% to about
65%,
or from about 60% to about 80%, ethanol by weight or by volume. It can be
eaten or drunk
by humans or by animal for nutrition or pleasure.
Non-limiting examples of alcoholic food products include, alcoholic liquids
comprising a base material such as water, juice, e.g., fruit or vegetable
juice, and milk and
alcohol. Alcoholic liquid products include, for example, beverages such as
beer, wine,
spirit and the like. Solid or semi-solid alcoholic products are edible foods
that contain
alcohol, for example, foods that have been cooked, combined and/or mixed with
alcohol.
Such alcohol-containing solid or semi-solid products are exemplified by meat,
fish,
6
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
chicken, fruits, breads, soups, stews, sauces, fondues, backed desserts such
as cakes,
pastries such as cookies and pies, and no-bake desserts such as creams, ice-
cream, puddings
and mousses, extract flavoring such as pure vanilla extract and pure almond
extract, filled
candies such as filled chocolate, snacks and food flamed with alcohol.
In some embodiments, a contemplated alcoholic food product is an alcoholic
beverage.
The terms "enriched alcoholic food product" and "enriched alcoholic beverage"
as
used herein refer to an alcoholic food product or alcoholic beverage,
respectively, enriched
by the addition thereto, provision thereto, mixing thereof, or combining it
with at least one
neurotransmitter and/or at least one neurotransmitter precursor. "Enrichment"
of the
alcoholic food products or alcoholic beverages contemplated herein is further
meant herein
enriching the product with desired qualities imparted to it by enriching it
with at least one
neurotransmitter and/or a precursor thereof.
The term "one or more neurotransmitter precursor" as used herein is
interchangeable with the term "at least one neurotransmitter precursor" and
means at least
one precursor of at least one neurotransmitter.
Neurotransmitters and precursors thereof
The action of alcohol is biphasic, when blood alcohol concentration (BAC)
levels
are rising, the stimulant properties of alcohol are more pronounced; when BAC
levels are
falling, the depressant effects of alcohol are more pronounced. Alcohol, for
example,
ethanol, being a small molecule, can interact with many neurotransmitter
systems in the
brain. It directly affects brain chemistry by altering levels of
neurotransmitters. Alcohol
affects both "excitatory" neurotransmitters and "inhibitory" neurotransmitters
and, hence,
has the properties of both a stimulant and a depressant. This makes the action
of alcohol in
the brain very different from, and much more complex than, large molecules
such as
opiates, tetrahydrocannabinol (THC), or amphetamine, which simulate a specific
neurotransmitter and interact with a specific neurotransmitter system.
Neurotransmitters play a key role in the function of the central nervous
system,
being chemical "messengers" that transmit signals throughout the body, signals
such as
those controlling thinking processes, behavior and emotion. Neurotransmitters
are excreted
to, and travel through, the synapses, those extremely small gaps between the
axon terminal
7
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
of neurons that release neurotransmitters in response to an impulse, and the
membrane of
adjacent axons, dendrites, muscle or gland cells having the appropriate
receptors for
binding the neurotransmitters. Neurotransmitters can either prompt or suppress
the further
signaling of nearby neurons. The main neurotransmitters include
norepinephrine,
epinephrine, serotonin, dopamine, endorphin, acetylcholine, gamma-aminobutyric
acid
(GABA), glycine, glutamic acid, aspartic acid, and taurine, the first six of
which are
neurotransmitters synthesized from amino acids, and the last three are amino
acids per se.
The term "neurotransmitter precursor", as used herein, refers to a substance
that
can be converted into a neurotransmitter in the body, particularly in the
brain, usually
through enzymatic reactions such as metabolic processes. For example, 5 -
hydroxytryptophane is a serotonin precursor.
Neurotransmitters which may be directly or indirectly affected by alcohol
include,
for example, GABA, endorphins, glutamate, dopamine, norepinephrine and
adrenaline
(epinephrine).
Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter, which
reduces energy levels and calms everything down. Drugs like Xanax and Valium
increase
GABA production in the brain, resulting in sedation. Alcohol increases the
effects of
GABA and affects the GABA system in a manner similar to valium leading to
relaxation
and drowsiness. Alcohol's effect on the GABA system may also be responsible
for its
depressant effects.
Glutamate is an excitatory neurotransmitter which normally increases brain
activity
and energy levels. Alcohol suppresses glutamate levels probably by inhibiting
the N-
methyl-d-aspartate (NMDA) glutamate receptor, resulting in a slowdown along
the brain's
highways. It is alcohol's effects on the glutamate system which lead to
staggering, slurred
speech, and memory blackouts.
Alcohol may exert depressant effects because it suppresses the excitatory
neurotransmitter glutamate and increases the inhibitory neurotransmitter GABA.
What this
means is that the thought, speech and movements of a person consuming alcohol
are slowed
down, and the more alcohol is consumed the more of these effects will be felt
(hence the
stumbling around, falling over chairs and other clumsy things drunk people
do). Cerebral
cortex is this region in the brain where thought processing and consciousness
are centered,
8
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
alcohol depresses the behavioral inhibitory centers, making the person less
inhibited; it
slows down the processing of information from the eyes, ears, mouth and other
senses; and
it inhibits the thought processes, making it difficult to think clearly.
Alcohol also affects
the cerebellum, the center of movement and balance in the brain, resulting in
the staggering,
off-balance swagger often associated with the so-called "falling-down drunk."
Endorphins are produced in response to certain stimuli, especially stress,
fear or
pain. They originate in various parts of the body such as the pituitary gland,
spinal cord
and throughout other parts of the brain and nervous system and interact mainly
with
receptors in cells found in regions of the brain responsible for blocking pain
and controlling
emotion. Alcohol affects the endorphin system in a manner similar to opiates,
acting as a
pain-killer and giving an endorphin "high".
Alcohol increases the release of dopamine (interchangeable herein with "DA"),
adrenaline and norepinephrine.
Adrenaline (epinephrine) and its precursor norepinephrine (noradrenalin), are
important hormones produced by the adrenal gland. They increase the heart
rate, blood
pressure, and blood glucose levels, open up the airways in the lungs and, like
cortisol, help
inhibit non-essential bodily functions. Alcohol causes the adrenal glands to
release
adrenaline and norepinephrine which ultimately enter the brain and promote
alertness and
"fight response". This is one reason why alcohol acts as stimulant.
Dopamine, 3,4-dihydroxyphenethylamine, is an
organic chemical of
the catecholamine and phenethylamine families having the chemical structure:
H 0,,,,,.,;.,,,,,,,-,,,,, NH 2
HO
This amine is synthesized by removing a carboxyl group from its precursor
levodopa (L-dopa; dihydroxyphenylalanine), which is synthesized in the brain
and kidneys
during the metabolism of the amino acid tyrosine. It is a neurotransmitter in
itself, and
a precursor of the hormone neurotransmitters epinephrine and norepinephrine.
Two main
brain areas produce dopamine that relays signals that travel throughout the
brain:
the substantia nigra, a tiny strip of tissue on either side of the base of the
human brain
(situated in a region known as the midbrain), and the close by ventral
tegmental area.
Dopamine from the substantia nigra helps in movements and speech. Dopamine,
thus,
9
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
helps regulate movement and emotional responses. When the brain cells that
make
dopamine in this area start to die off, a person can have trouble initiating
movement.
The ventral tegmental area usually sends dopamine into the brain when animals
or
human expect or receive a reward, and helps control the brain's reward and
pleasure
centers. The reward center (also known as the "reward pathway") is comprised
primarily
of the nucleus accumbens (NAc), the ventral tegmental area (VTA), and a part
of the
prefrontal cortex. This combination of brain areas which form the reward
center is affected
by virtually all pleasurable activity, including everything from hanging out
with friends,
going on vacation, ingesting drugs (e.g., cocaine), listening to music, eating
and drinking,
having sexual activity, and consuming alcohol. All things which give us
pleasure, cause a
release of dopamine in the reward pathway as well as trigger a number of other
events in
the brain including endorphin release and activation of the orbitofrontal
region of the
prefrontal cortex. Dopamine is known as the "motivation molecule" or the
"reinforcement
molecule" as it is responsible for reward-seeking behavior and helps provide
the drive,
focus and concentration needed to get things done. This dopamine release tells
the brain
that whatever it just experienced is worth getting more of, and that helps
animals and
humans change their behaviors in ways that will help them attain more of the
rewarding
item or experience. This brain reward system is associated with "feeling good"
and
promotes survival of the species by rewarding behaviors necessary for
continued survival.
Dopamine is also involved in many other functions of the brain including motor
activity, motivation, learning, pain processing, mood, attention span and
regulation of
sleep. It regulates stress relief.
Lowering dopamine can make animals and humans lose pleasure in activities like
eating and drinking. This joyless state, where animals or human no longer find
pleasure in
activities they used to enjoy and are no longer motivated to do those
activities, is called
anhedonia. People with some mental illnesses, such as depression and
schizophrenia, may
experience anhedonia as part of their disease.
Dopamine deficiency results in Parkinson's Disease, and people with low
dopamine
activity may be more prone to addiction. Alcohol as well as all drugs which
lead to
dependence appear to affect the dopamine system. Stimulants like amphetamine
and
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
cocaine affect dopamine directly whereas alcohol and other drugs appear to
affect it
indirectly.
Alcohol consumption triggers a boost of dopamine release. Alcohol does not
lead
to an increase of dopamine throughout the brain; it only causes an increase in
dopamine in
the reward center, leading to the relaxing and carefree experience of the
alcohol "buzz".
Consumption of even small amounts of alcohol increases the amount of dopamine
in the
NAc in a dose-response manner. Alcohol increases DA via the promotion of
synaptic
terminal DA release rather than via the inhibition of DA transporters. Alcohol
can also
indirectly increase DA levels by affecting the GABA system and the endorphin
system.
Neurons from the GABA system extend into the reward pathway and when alcohol
affects
the GABA system these neurons release dopamine into the reward pathway.
Likewise,
neurons extend from the endorphin system into the reward pathway and these
also release
dopamine into the reward pathway when alcohol directly stimulates the
endorphin system.
It is unlikely that the increase in dopamine alone is responsible for the
stimulant
properties of alcohol. It is most likely that the stimulating effects of
alcohol are due to its
effects on adrenaline, norepinephrine, and the prefrontal cortex as well.
A boost in the activation of Dopaminergic pathways eventually causes a
depletion
of the dopamine reserves within the brain cells, leaving the brain in an
imbalanced state.
As Dopamine itself is impenetrable to the blood-brain barrier, it must
synthesized in situ
from its precursors. Over time, with more drinking, the dopamine effect
diminishes until
its almost nonexistent.
It has been postulated by the present inventor that kicking-off brain DA
release via
alcohol consumption, and simultaneously providing means to sustain elevated
brain DA
level by providing DA building blocks, may enhance the euphoric feeling and
afford
qualities such as increased motivation, focus and concentration to pursue
rewarding actions
such as working and learning, increased sociability, and attention, while at
the same time
alleviating alcohol withdrawal symptoms and, moreover, substantially
decreasing
addiction disposition.
The present inventors envisaged, and successfully practiced enriched alcoholic
food products, for example, enriched alcoholic beverages, containing a
precursor of DA,
for example, tyrosine, and, optionally, a psychostimulant substance such as
caffeine, based
11
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
on their strong affiliations to the metabolism of DA within the brain, thereby
promoting
DA synthesis within the central nervous system and establishing a long lasting
steady state
of readily available DA. This sustained supply of DA building blocks from the
very first
moment of alcohol intake, may increase the positive and enjoyable effects of
alcohol
consumption, while neutralizing negative effects associated with DA depletion
followed
by it.
Furthermore, enhancement of the positive effects of alcohol may help reduce
the
risk of alcohol abuse. Motives of alcohol consumption are classically
"enhancing motives"
(drinking to enhance positive and social mood) and "coping motives" (drinking
to cope
with negative mood). While enhancing drinkers enjoy the positive effects of
alcohol
consumption, coping drinkers rely on its sedative effects, and are strongly
exposed to risks
of alcohol abuse and alcoholism. Through the enhancement of alcohol's positive
effects
and the negation of its sedative effects, provided herein is a method to
reduce risks of
alcohol abuse amongst coping drinkers.
In some embodiments, the alcoholic products described herein are designed to
promote at least the levels of dopamine, endorphin norepinephrine and/or
epinephrine in
the brain. To this end, the alcoholic products are enriched with one or more
neurotransmitters and/or neurotransmitters precursors.
For example, L-phenylalanine (Phe), L-tyrosine (Tyr) and/or levodopa (L-dopa)
are
the precursors of dopamine and other catecholamines such as norepinephrine and
epinephrine.
The terms "dopamine precursor" and "dopamine immediate metabolic precursor"
as used herein are interchangeable and refer to a substance that can be
converted into
dopamine in the body through a series of one or more metabolic reactions.
The primary and minor metabolic pathways for obtaining DA from its precursors
are:
Primary: Phe ¨> Tyr ¨> levodopa ¨> DA
Minor: Phe ¨> Tyr ¨> p-Tyramine ¨> DA
Minor: Phe ¨> m-Tyrosine ¨> m-Tyramine ¨> DA
The direct or immediate metabolic precursor of dopamine, L-dopa, can be
synthesized indirectly from the essential amino acid Phe or directly from the
non-essential
12
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
amino acid Tyr. Additionally or alternatively in can be supplemented form
plants (e.g.
legumes) and animals. Most of the levodopa is immediately broken down (e.g.,
in the
intestine) before it enters the brain
primarily by decarboxylase
enzymes and catecholamine-0-methyltransferase (COMT).
L-Phenylalanine is converted into Tyr by the enzyme phenylalanine hydroxylase,
with molecular oxygen (02) and tetrahydrobiopterin (THB) as cofactors. L-
Tyrosine is
converted into L-dopa by the enzyme tyrosine hydroxylase, with
tetrahydrobiopterin, 02,
and iron (Fe2 ) as cofactors. L-dopa is converted into dopamine by the
enzyme aromatic L-amino acid decarboxylase (also known as dopa decarboxylase),
with pyridoxal phosphate (the active form of vitamin B6) as the cofactor.
Dopamine is converted into norepinephrine by the enzyme dopamine 0-
hydroxylase, with 02 and L-ascorbic acid (vitamin C) as cofactors.
Norepinephrine is
converted into epinephrine by the enzyme
phenylethanolamine N-
methyltransferase with S-adenosyl-L-methionine (SAMe) as the cofactor.
In some embodiments, the enriched alcoholic food product provided herein may
increase DA brain level. In some embodiments, the enriched alcoholic product
may afford
continued elevated DA levels in the brain initiated by alcohol consumption, to
thereby
provide at least some of the desired benefits exerted by dopamine release, for
example
joyful and euphoric feeling, and relaxation. In the context of any of these
embodiments, a
disclosed enriched alcoholic food product may comprise or may be supplemented
with DA
and/or one or more DA precursors.
Without wishing to be bound by theory, it is assumed that when the enriched
alcoholic food product, e.g. an alcoholic beverage, is consumed, the alcohol
in the product
causes an immediate release of dopamine. A dopamine precursor contained in the
product,
reinforces the neurotransmitter supply in the brain, thereby maintaining or
even amplifying
its level for a prolonged period of time. This prolonged and sustained level
of
neurotransmitters in the brain, which last long after the alcohol level in the
blood has gown
down to zero, affords not only a prolonged euphoric feeling but, moreover,
quenches or
circumvent the unpleasant psychological and physiological sensations
associated with
alcohol withdrawal such as headache, nausea and depression. These effects
outgo the
psychotropic effects associated with consumption of high amounts of alcohol
alone.
13
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
In some embodiments, supplementing an alcoholic food product, for example,
alcoholic beverage such as beer or wine, with precursors of neurotransmitters
as provided
herein, enriches the alcoholic food product and imparts to it at least the
following positive
psychoactive effects: blissful, joyful and euphoric sensation. The term
"psychoactive" as
used herein means affecting the mood, and "positive psychoactive effect"
herein means
affect the mood is a positive, desired manner.
Positive psychoactive effects exerted by the enrich alcoholic food product
provided
herein may sustain long after consumption of the product, and it may not be
accompanied
by drunkenness or intoxication. In some embodiments, the euphoric feeling
lasts from
about 5 minutes up to 24 hours post consumption, with almost no accompanying
feeling of
intoxication. For example, a euphoric state of mind may last about 5-10 min,
about 10-15
mm, about 10-20 mm, about 20-30 min, about 30-40 min, about 40-50 min, 0-1
hours,
about 1-3 hours, about 1-4 hours, about 2-5 hours, about 3-5 hours, about 4-6
hours, about
5-8 hours, about 5-9 hours, about 6-10 hours, about 7-10 hours, about 8-11
hours, about 9-
hours, about 9-11 hours, about 9-15 hours, about 10-12 hours, about 12-15
hours, about
15-18 hours, about 15-20 hours, about 18-22, about 20-24 hours, or even
longer, after blood
alcohol level has already dropped to zero.
One of the unique and unexpected properties of the enriched alcoholic food
product
provided herein, e.g., an alcoholic beverage, is that it does not dim the
consumer's sense
of alertness as often happens upon alcohol consumption, but to contrary: the
enriched
alcoholic food product provided herein keeps the consumer well and sharply
focused, fully
conscious, in-control and with the ability to remain concentrated for extended
periods,
contrary to the psychotropic effects exerted by regular alcoholic products
particularly
alcoholic beverages. In fact, the enriched alcoholic product provided herein
affords to the
consumer a better, higher and prolonged focusing and concentration abilities
in spite the
alcohol it contains.
The term "psychotropic", as used herein, means the ability to influences the
mind
or cognitive abilities of a person, and/or to affect mental processes (e.g.,
emotions,
perception) and mental activity (e.g., behavior). The term "positive
psychotropic effects"
herein means affect the mind, mental and/or the cognitive abilities is a
positive, desired
manner.
14
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
In some embodiments, supplementing an alcoholic food product, for example,
alcoholic beverage such as beer or wine, with one or more neurotransmitters
and/or one or
more precursors of neurotransmitters as described herein, enriches the
alcoholic food
product by imparting to it the ability to exert at least the following
positive psychotropic
effects: (i) higher motivation e.g., to work, learn and take part in rewarded
activities; (ii)
improved concentration and focus; (iii) higher self-confidence; (iv)
arousal;
(v) wakefulness; (vi) elevated alertness; (vii) improved creativity and
creative thinking
(viii) curiosity and openness to new experiences; (ix) sense of self-
fulfillment, self-
contempt; (x) relaxation; (xi) improved capacity to switch attention
efficiently between
tasks; (xii) improved sociability and extroversion behavior (xiii) better
cognitive and/or
mental function; and (xiv) emotional and physical sense of well-being.
The positive psychotropic effects exerted by an enriched alcoholic food
product
may last hours and even days after consumption thereof. In some embodiments, a
positive
psychotropic effect, for example, higher motivation, or improved ability e.g.,
to concentrate
and maintain focused, alert, awaken, self-confident and/or improved
sociability lasts from
minutes to about 72 hours after consuming the enriched alcoholic food product.
For example, a person consuming e.g., an enriched alcoholic beverage such as
beer
or wine may experience higher motivation to conduct rewarding activities,
improved
sociability, better cognitive and/or mental or emotional function, and/or
physical sense of
well-being, from about 5 min to about 10 min, from about 8 mm to about 15 mm,
from
about 10 min to about 20 min, from about 25 min to about 40 min, from about
0.5 hour to
about 2 hours, from about 1.5 hours to about 4 hours, from about 2 hours to
about 5 hours,
from about 3 hours to about 6 hours, from about 4 hours to about 7 hours, from
about 4
hours to about 8 hours, from about 5 hours to about 8 hours, from about 6
hours to about 9
hours, from about 6 hours to about 10 hours, from about 7 hours to about 12
hours, from
about 9 hours to about 15 hours, from about 8 hours to about 16 hours, from
about 10 hours
to about 15 hours, from about 15 hours to about 20 hours, from about 18 hours
to about 22
hours, from about 20 hours to about 25 hours, from about 25 hours to about 35
hours, or
even from about 35 hours to about 48 hours, after consuming the beer or wine
enriched
with one or more neurotransmitter and/or precursors thereof.
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
In some embodiments, a person consuming e.g., an enriched alcoholic beverage
such as beer, wine or spirit may experience higher motivation, better or
improved creative
thinking, concentration, wakefulness, self-confident and/or joyful self-
contentment that
lasts from about 0.25 day to about 0.5 day, from about 0.5 day to about 0.75
day, from
about 0.5 day to about 1.0 day, from about 0.5 day to about 1.25 days, from
about 0.75 day
to about 1.0 day, from about 1.0 day to about 1.5 days, from about 1.5 days to
about 2.0
days, from about 1.5 days to about 2.5 days, from about 2.0 days to about 2.5
days, or from
about 2.5 days to about 3.0 days, and even longer, after consuming the beer,
wine or spirit
enriched with one or more neurotransmitter and/or precursors thereof.
In some embodiment, a disclosed enriched alcoholic food product comprises
dopamine and/or one or more dopamine precursors.
In some embodiments, a disclosed enriched alcoholic food product comprises at
least one dopamine precursor.
For example, elevated levels of DA conferred or induced by a contemplated
enriched alcoholic food product may enhance the expectation of pleasure in a
person
consuming the product.
A contemplated alcoholic food product enriched, for example, with one or more
DA precursors, for example Tyr, may positively affect memory and learning, as
dopamine
activity in the brain plays a substantial part in memory and learning. It is
essential for long-
term memory storage and retrieval. Dopamine further signals important events:
it helps
remembering events that have motivational significance. This ensures that
memories are
relevant and accessible for future behavior. Dopamine also plays an essential
role in
working memory. Working memory is the capacity to use information from short-
term
memory for guiding one's own actions.
For example, a contemplated alcoholic food product enriched with one or more
DA
precursors may positively affect focus and attention. Moderate levels of
dopamine (not too
high or too low) improve the capacity of individuals to switch attention
efficiently between
tasks. Furthermore, moderate levels of dopamine direct attention more
efficiently to stimuli
that are relevant to ongoing tasks.
For example, a contemplated alcoholic food product enriched with one or more
DA
precursors may positively affect pathways associated with social and
extroversion behavior
16
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
and/or with forming romantic attachments. Intense romantic love is associated
with the
dopamine reward system, and the crosstalk between oxytocin, the "love
molecule", and
dopamine.
A contemplated alcoholic product enriched with one or more DA precursors may
further confer or bestow to the consumer one or more of the following benefits
or effects:
(a) controlled sleep-wake cycle. Dopamine D1 receptor (DRD1) activation
induces
arousal and wakefulness;
(b) increased creativity. Dopamine is involved in cognitive flexibility - one
of the
main components of creativity and creative thinking. Dopamine is also
responsible for
openness to new experiences, another factor associated with creativity;
(c) stimulated sexual drive. A person's response to sex, just like other
rewards, is
largely dependent on DA. Erections are dependent upon activation of both
dopaminergic
neurons (ventral tegmental area) and dopamine receptors (NAc); and
(d) depression amelioration. Elevated DA levels exerted by a disclosed product
may
ameliorate mental conditions related to low DA levels, such as hopelessness,
worthlessness, stress handling, lack of interest in life, decreased
motivation,
procrastination, inability to feel pleasure, altered sleep patterns, mood
swings, and
impulsive or self-destructive behaviors.
In exemplary embodiments the neurotransmitter precursor or the DA precursor of
a contemplated enriched alcoholic food product is L-tyrosine (Tyr).
In some embodiments, the enriched alcoholic product is an alcoholic beverage
supplemented with at least one neurotransmitter precursors which is a DA
precursor
selected from Phe, Tyr or L-dopa.
In exemplary embodiments, the dopamine precursor supplemented to the beverage
is Tyr.
The amounts of tyrosine provided to the alcoholic beverages described herein
is
determined depending on some variables, for example, the amount of alcohol in
the
beverage, the amount and type of other supplements in the alcoholic beverage
that may
cross react with tyrosine, and the amount and type of other supplements
provided to the
beverages that may further promote elevated levels of dopamine. Usually, the
amount of
Tyr is in the range of 10 mg to 5000 mg per 1 liter of beverage, for example,
from about
17
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
mg to about 30 mg, from about 20 mg to about 50 mg, from about 30 mg to about
60
mg, from about 50 mg to about 70 mg, from about 50 mg to about 100 mg, from
about 100
mg to about 150 mg, from about 150 mg to about 200 mg, from about 100 mg to
about 250
mg, from about 200 mg to about 400 mg, from about 200 mg to about 300 mg, from
about
200 mg to about 500 mg, from about 300 mg to about 400 mg, from about 300 mg
to about
700 mg, from about 400 mg to about 800 mg, from about 500 mg to about 900 mg,
from
about 500 mg to about 1000 mg, from about 800 mg to about 1000 mg, from about
900 mg
to about 1100 mg, from about 1000 mg to about 1200 mg, from about 1000 mg to
about
1500 mg, from about 1000 mg to about 1600 mg, from about 1500 mg to about 2000
mg,
from about 2000 mg to about 3000 mg, from about 3000 mg to about 4000 mg, or
from
about 4000 mg to about 5000 mg per liter, and any intermediate ranges
therebetween.
In exemplary embodiments, the amount of tyrosine is about 350 mg/L, about 500
mg/L, about 750 mg/L or from about 100 mg/L to about 1000 mg/L.
Psychostimulant substances
The enriched alcoholic food products described herein may further comprise
supplements that promote or support increased level of a neurotransmitter such
as, but not
limited to, norepinephrine, serotonin, dopamine, endorphin, acetylcholine,
GABA, glycine,
glutamic acid, aspartic acid, and/or taurine.
The terms "psychostimulant supplement" and "psychostimulant substance", herein
used interchangeably, refer to an edible substance that has a direct or
indirect effect in
increasing the levels of one or more neurotransmitters in the body,
particularly in the brain,
or in maintaining elevated neurotransmitter levels brought about, for example,
by in situ
conversion of a neurotransmitter precursor into a neurotransmitter, and/or by
consuming
alcohol. A psychostimulant substance may be directly or indirectly involved in
enhancement of neurotransmitter synthesis and/or neurotransmitter stability,
or
upregulation of a neurotransmitter, for example, by upregulating enzymes that
synthesize
the neurotransmitter or protect the neurotransmitter from metabolic
degradation. A
psychostimulant substance may, additionally or alternatively, be directly or
indirectly
involved in inhibition of neurotransmitter reuptake and/or neurotransmitter
degradation,
for example, by inhibiting or down regulating a neurotransmitter metabolic
enzyme.
18
RECTIFIED SHEET (RULE 91)
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Psychostimulant substances may further foods which supply building blocks for
production
of a neurotransmitter or a precursor thereof.
In some embodiments, a psychostimulant substance increases metabolism rate in
the body, thereby increasing metabolic conversion of a neurotransmitter
precursor into a
neurotransmitter.
In some embodiments, a psychostimulant substance inhibits or blocks metabolic
enzymes that degrade a neurotransmitter precursor in the blood stream or in
the digestive
system.
Non-limiting examples of psychostimulant substances include caffeine, omega-3,
fatty acids such as docosahexaenoic acid (DHA), magnesium, soluble fibers,
folate, olive
oil or monounsaturated fats extracted therefrom, green tea or theanine
extracted therefrom,
pregnenolone and any derivative thereof, uridine, iron, spices such as
turmeric or curcumin
extracted therefrom, Rhodiola rosea or an extract thereof, oregano or an
extract thereof,
co-factors, vitamins such as vitamin C and vitamin B6, minerals and the like.
Caffeine is the most widely consumed psychostimulant substance. It is known to
highly effects the metabolism within the central nervous system via the
blockade of
adenosine receptors, which modulate the neurotransmission of glutamate,
serotonin,
acetylcholine and dopamine. Caffeine itself has a wide variety of effects on
the
dopaminergic system, which is crucial for the expression of caffeine's
stimulating
properties. Furthermore, caffeine promotes tyrosine hydroxylase activation via
cellular
Ca2+ entry stimulation mechanism, and it has been shown that chronic caffeine
intake
increases tyrosine hydroxylase mRNA expression. As tyrosine hydroxylase is the
rate-
limiting enzyme in the biosynthesis of DA and other catecholamines, caffeine
may
accelerates DA synthesis through upregulation of this enzyme. Caffeine may
provide an
energy boost just like sugar and alcohol. However, caffeine alone indirectly
promotes DA
level elevation only temporarily.
Without being limited by theory, it is assumed that providing caffeine and
alcohol
together with a supply of DA precursors such as tyrosine, phenylalanine and/or
any other
DA precursor, may enable enhanced and continued conversion of immediate
metabolic DA
precursors to DA, thus affording stable elevated levels of DA in the brain for
a prolonged
time, hence a prolonged duration of desired psychotropic and/or psychoactive
effects such
19
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
as euphoric and bliss feelings, high motivation and energy, that would last
long after
consumption of alcohol ceased.
In an enrich alcoholic food product, for example, a liquid product, the amount
of
caffeine may range from about 0 mg to about 2 gr per 1 liter of beverage. For
example,
from about 5 mg/L to about 10 mg/L, from about 10 mg/L to about 20 mg/L, from
about
mg/L to about 50 mg/L, from about 50 mg/L to about 80 mg/L, from about 60 mg/L
to
about 100 mg/L, from about 200 mg/L to about 300 mg/L g, from about 200 mg/L
to about
400 mg/L, from about 300 mg/L to about 500 mg/L, from about 500 mg/L to about
800
mg/L, from about 600 mg/L to 900 mg/L, from about 700 mg/L to 750 mg/L, from
about
800 mg/L to about 1000 mg/L, from about 800 mg/L to about 1200 mg/L, from
about 900
mg/L to about 1200 mg/L, from about 1100 mg/L to about 1400 mg/L, from about
1200
mg/L to about 1500 mg/L, from about 1500 mg/L to about 1700 mg/L, from about
1500
mg/L to about 2000 mg/L, or from about 1700 mg/L to about 2000 mg/L.
In certain embodiments, liquid alcoholic food products described herein
contain
from about 10 mg/L to about 1200 mg/L, for example, about 35 mg/L about 50
mg/L, about
100 mg/L or 350 mg/L of caffeine.
In exemplary embodiment an enriched beer is provided comprising a DA precursor
such as tyrosine and a psychostimulant substance such as caffeine.
A contemplated enriched beer, for example, can contain Tyr and about 0.75
mg/ml
caffeine and yet maintain the original taste, aroma, palatability and gas
content of a beer
with no hint for caffeine's dominant bitter taste.
Enriched beers as well as other enriched alcoholic beverages provided herein,
provide the exact combination of alcohol, DA precursor such as tyrosine and
psychostimulant substance such as caffeine, that affords an optimal rate of
brain dopamine
level increase, as well as optimal, stable DA level that provide to the
consumer intensified,
long lasting pleasure and a pleasant drinking experience, while circumventing
the "down"
feeling often associated with alcohol consumption.
Certain minerals and B-vitamins, especially zinc, vitamin B6, and folate, are
necessary for dopamine synthesis and neurotransmission. These nutrients are
often
depleted in individuals due to medications, inadequate diets, excessive
stress, and toxic
environmental exposures, compromising the ability to properly synthesize
RECTIFIED SHEET (RULE 91)
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
neurotransmitters like dopamine. Dopamine is easily oxidized, thus
antioxidants such as
vitamins C and E may assist in maintaining desired levels of DA.
Magnesium deficiency can cause decreased levels of dopamine, which might lead
to depression.
Pregnenolone is the main steroid produced from cholesterol mainly in the
brain,
gonads and adrenal glands. Pregnenolone and its sulfate (pregnenolone sulfate)
are
excitatory neurosteroids, i.e., they stimulate the brain, and can increase DA.
Pregnenolone
and/or its derivatives have anti-stress and mood-elevating effect, they
enhance learning and
memory and increase the amount of deep sleep, improve energy, vision, clarity
of thinking,
wellbeing, and often sexual enjoyment or libido.
The amount of pregnenolone and derivatives thereof, particularly pregnenolone
sulfate, in, e.g., a liquid alcoholic product described herein is in the range
of from about 0
mg to 3.0 mg per liter, for example 0.1-0.5 mg/L, or about 1 mg/L.
Curcumin is known to be the most active phytochemical in yellow dietary spice
turmeric. Curcumin has been proven to have anti-oxidant, anti-inflammatory,
anti-
microbial, hypoglycemic, anti-rheumatic, wound healing and anti-cancer
activities.
Curcumin further possesses antidepressant properties by way of interacting
with dopamine
receptors and increasing brain dopamine levels. For example, curcumin
increases DA
concentration in the brain by inhibiting monoamine oxidase (MAO)-mediated DA
break
down. Curcumin may be taken daily in large amounts, even up to 8 gr/day.
The amount of curcumin in, e.g., liquid alcoholic product described herein is
in the
range of from about 0.1 mg/ml to 2.0 g/ml, for example about 0.2-0.5 g/ml.
L-theanine is an amino acid uniquely found in green tea that creates an alert
state
of relaxation without drowsiness. L-theanine is known to be able to cross the
blood-brain
barrier and increase dopamine levels in the brain. As such, it may have anti-
depressant and
anti-anxiety effects, it may reduce mental and physical stress, and lead to
improvements in
learning and memory in humans and animals. Even just a single, small dose of L-
theanine
(100 mg) significantly improves the ability to pay attention and maintain
focus.
The amount L-theanine e.g., in a liquid alcoholic product in accordance with
some
embodiments, is in the range of from about 0 mg to about 2000 mg per 1 liter
of beverage,
for example, from about 10 mg/L to about 30 mg/L, 20 mg/L to about 50 mg/L, 50
mg/L
21
RECTIFIED SHEET (RULE 91)
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
to about 100 mg/L, 80 mg/L to about 150 mg/L, 100 mg/L to about 150 mg/L, 150
mg/L
to about 200 mg/L, 150 mg/L to about 400 mg/L, 300 mg/L to about 500 mg/L, 550
mg/L
to about 750 mg/L, 500 mg/L to about 1000 mg/L, 700 mg/L to about 1200 mg/L,
1100
mg/L to about 1250 mg/L, 1200 mg/L to about 1500 mg/L, 1550 mg/L to about 1850
mg/L,
or 1700 mg/L to about 1000 mg/L.
In certain embodiments, enriched alcoholic beverages described herein contain
600
mg/L, 1200 mg/L or 1800 mg/L of L-theanine.
Rhodiola rosea, or "golden root," is a popular plant in traditional medicine
in
Eastern Europe and Asia, with a reputation for improving depression, enhancing
work
performance, eliminating fatigue and treating symptoms resulting from intense
physical
and psychological stress. Rhodiola exerts its benefits via multiple effects on
the central
nervous system, including enhancing the stability of dopamine and supporting
its reuptake.
This leads to notable decreases in depression, anxiety, and fatigue, as well
as an increased
ability to handle stress.
Rhodiola extract derived from Rhodiola rosea root and standardized to contain
3%
total rosavins and a minimum 1% salidrosides may be included in, e.g.,
enriched liquid
alcoholic product described herein in amounts which range from about 300 mg to
about
2000 mg per liter, for example, 510 mg/L, 800 mg/L or 1100 mg/L.
Other psychostimulant substances contemplated herein include, for example,
nutritional or brewer's yeasts which is rich in uridine-5w-monophosphate that
may increase
DA levels in the brain; oregano, which increases DA levels by decreasing DA
break down
and reuptake; and resistant starch, a type of soluble fiber that increases
butyrate, which
may increase dopamine levels.
In some embodiment, a disclosed enriched alcoholic food product comprises one
or more psychostimulant substances that directly or indirectly affect DA brain
level, for
example, caffeine, theanine, curcumin, uridine, pregnenolone, and/or oregano.
The amounts of psychostimulant substance provided to the enrich alcoholic
products described herein vary and depend on the psychostimulant substance
itself as well
an on the other ingredients provided to the enriched alcoholic product,
particularly to the
amount of alcohol, the amount and type of DA precursor(s), the presence of
other
neurotransmitter or precursors thereof, and/or the amount and type of other
supplements
22
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
that may cross react or enhance the effect of a particular psychostimulant
substance. Excess
dopamine is dangerous and needs to be avoided, and a skilled person would
appreciate that
the amount and number of psychostimulant substances provided to the alcoholic
beverages
are to be adjusted so as to avoid secretion, production and/or otherwise
promotion of excess
DA.
The amount of one or more psychostimulant substances in a contemplated
enriched
alcoholic food product may be in a range of from 0 to about 10% by weight. For
example,
from about 0.01% to about 1.00%, from about 0.01% to about 1.00%, from about
0.05%
to about 1.00%, from about 0.1% to about 0.3%, from about 0.2% to about 0.5%,
from
about 0.5% to about 1.0%, from about 1.0% to about 3.0%, from about 1.0% to
about 5.0%,
from about 5.0% to about 10.0%, from about 8% to about 10.0%, by weight or by
volume
of total enriched alcoholic product, and any sub-ranges and/or individual
values
therebetween.
The amount of psychostimulant substances in a contemplated product are
adjusted
such that the original texture, smell and palatability of the product is
maintained.
Alcoholic beverages
In an aspect of the disclosure, there is provided an enriched alcoholic
beverage
comprising a base liquid, alcohol, one or more neurotransmitter and/or one or
more
neurotransmitter precursors as defined herein.
In some embodiments, a contemplated enriched alcoholic beverage optionally
further comprises one or more psychostimulant substances as defined herein.
In some embodiments, provided herein is enriched alcoholic beverage comprising
a base liquid, alcohol, dopamine and/or at least one dopamine precursor and,
optionally,
one or more psychostimulant substances as described herein, for example,
caffeine.
Herein throughout, the term "base liquid" describes a liquid form of a
substance or
a mixture of substances which either alone or when mixed with other additives
can form a
beverage. In some embodiments, the base liquid is a base beverage.
In some embodiments, the base beverage is an alcohol-free base beverage.
The phrase "alcohol-free base beverage", as used herein, is a beverage having
alcohol percentage that is no more than 50% of the alcohol content in a
corresponding
alcoholic beverage, preferably no more than 40%, no more than 30%, no more
than 20%,
23
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
no more than 15%, no more than 10%, no more than 5%, no more than 1%, no more
than
0.5%, no more than 0.1%, no more than 0.05%, or no more than 0.01%, of the
alcohol
content acceptable for a certain beverage, including any subranges and any
intermediate
values there between. This phrase is used herein as encompassing both base
beverages
that are typically used for forming alcoholic beverages, and base beverages
which are
typically used as non-alcoholic beverages, for example, juices.
In some embodiments, the alcohol-free base beverage is devoid of alcohol.
By "devoid of alcohol" is meant herein less than 0.01% or less than 0.005%, or
less
than 0.001%, of alcohol by volumes, or even null.
Exemplary alcohol-free base beverages which form the liquid base for the
enriched
alcoholic beverages described herein include, but are not limited to, natural
or artificially
flavored fruit juice (such as grape, mango, elder, apple, orange juice, and
the like),
vegetable juice, fruit syrup, concentrate or nectar from fruits, plant
materials such as agave,
jello, carbonated beverages such as cola, optionally with addition of roasted
malt beer,
caffeinated beverages, specialized flavor formulations emulating the taste of
existing wines
and spirits, non-alcoholic cocktails ("mocktails"), malt beer, dealcoholized
ciders,
dealcoholized wines, dealcoholized beers, dealcoholized spirits, tonic water
and water.
When the liquid base comprises alcohol, it is termed herein a "base alcoholic
liquid". In some embodiments, the base alcoholic liquid is an alcoholic
beverage. The term
"alcoholic beverage" as used herein encompasses any beverage having an alcohol
(ethanol)
content of at least 2% by volume, whether distilled, fortified, brewed, or
produced by
fermentation, and includes, but is not limited to, wine, beer, fermented
liquids derived in
whole or in part from fruit juices, such as cider and perry (pear cider),
spirits, flavored
alcoholic beverages collectively termed herein and in the art as "alcopops",
and the like.
In some embodiments, the base alcoholic liquid is an alcoholic beverage
substitute
that has residual alcohol content of 0-20% by volume, depending on the
alcoholic beverage
being substituted.
Embodiments described herein provide an enriched alcoholic beverage comprising
a base alcoholic liquid, one or more neurotransmitter and/or one or more
neurotransmitter
precursors as defined herein.
24
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
In some embodiments, a contemplated enriched alcoholic beverage optionally
further comprises one or more psychostimulant substances as defined herein.
In some embodiments, provided herein is enriched alcoholic beverage comprising
a base alcoholic liquid, dopamine and/or at least one dopamine precursor as
described
herein and, optionally, one or more psychostimulant substances as described
herein.
Any combination of the base liquid, base alcohol-free liquid and base
alcoholic
liquid as described herein is contemplated for the enriched alcoholic
beverages described
herein.
The contemplated enriched alcoholic beverages provided herein provide the
drinker
with the palatability effect of common alcoholic beverages, and further
provide the drinker
with a sustained euphoric feeling, pleasure and overall sensation of wellbeing
and vitality
which far exceed the effects provided by corresponding alcoholic beverages
which do not
contain these enriching supplements and additives. Moreover, unlike common
alcoholic
beverages, the enriched alcoholic beverages provided herein provide a
substantial relief of
the adverse effects associated with alcohol consumption, particularly the
"down" feeling
or depression associated with intoxication and sobering up.
A unique and surprising feature of the enriched alcoholic beverage provided
herein
is that they provide the drinker with intensified and prolonged pleasurable,
joyful, and
euphoric feelings accompanied with a boost of energy and motivation, while
affording a
substantial reduction in drunkenness symptoms.
Contemplated enriched alcoholic beverages provide substantial reduction of
intoxication effects, namely, they substantially minimize intoxication
effects. For example,
these beverages reduce intoxication by 10-95%, or minimize intoxication
effects to at least
5% of the effect associated with consuming a corresponding non-enriched
alcoholic
beverage having the same alcohol content.
In some embodiments, intoxication and/or other negative physical and emotional
feelings accompanying sobering up may be relieved, eased or alleviated by
about 0 to
100%. For example, alleviation of undesired effects exerted by a contemplated
enriched
alcoholic beverage may be up to 10%, up to 20%, up to 30%, up to 40 %, up to
50%, up to
60% up to 70%, up to 80%, up to 90%, up to 95%, or up to 100% as compared to a
corresponding non-enriched alcoholic beverage. The extent of intoxication
relief or
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
moderation changes form one person to another and depends on a collective of
variable
such as the person's tolerance to alcohol, the amount of alcohol in the
beverage or the
amount of beverage consumed. In some embodiments, the drinker does not
experience any
insobriety at all even though relatively high amount of alcohol is consumed,
for example,
at least 1 liter of enriched beer or at least 3 glasses of enriched wine.
Any combination of neurotransmitter precursors and psychostimulant substances
as described herein is contemplated herein.
Because the enriched alcoholic beverage of the present disclosure affords
palatability and psychotropic effect which outgo the effects of a
corresponding non-
enriched alcoholic beverages, these enriched beverages may be provided with
reduced
amounts of alcohol as compared to the corresponding non-enriched alcoholic
beverages.
For example, the alcohol amount in a contemplated enriched alcoholic beverages
may be
about 100%, about 95%, about 90%, about 80%, about 75%, about 70%, about 65%,
about
60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about
20%,
about 15%, about 10%, about 5%, about 3%, about 1% or about 0.5%, of the
amount of
alcohol in a corresponding non-enriched alcoholic beverage.
In some embodiments, the enriched alcoholic beverage is selected from enriched
beer, wine, cider, spirit and/or enriched alcopop beverage. In some
embodiments, these
enriched alcoholic beverages comprise one or more neurotransmitter precursors.
In
exemplary embodiments, the neurotransmitter precursor is a precursor of
dopamine, for
example, L-tyrosine.
The term "beer" as used herein and in the art means an alcoholic beverage
obtained
by malting and fermenting one or more of the cereal grains, and includes ale,
stout, porter
and lager. Typical alcoholic beer beverages include an alcoholic content of 3-
8%. Some
high-alcohol content beers comprise 8-12% alcohol, for example 10% alcohol.
In some embodiments, the beer is a "reduced alcohol beer", namely a beer as
defined herein comprising up to 3.5% alcohol, for example, up to 3.0%, up to
2.2%, up to
2.0%, up to 1.5%, up to 1.0%, up to 0.5%, up to 0.3%, up to 0.1%, up to 0.05%,
up to
0.01%, alcohol, or the beer may be devoid of alcohol.
Non-limiting examples of enriched beers provided in embodiments described
herein include:
26
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(i) Ale. A type of beer brewed using a warm fermentation method, resulting in
a
sweet, full-bodied and fruity taste. As with most beers, ale typically can
have a bittering
agent to balance the sweetness of the malt and act as a preservative. Ale is
usually bittered
with hops, the dried, cone-shaped flowers of the Mulberry plant used in the
beer-brewing
process to give a beer a bitter taste. Ale is typically fermented at
temperatures between 15
and 24 C (60 and 75 F). At temperatures above 24 C (75 F) the yeasts can
produce
significant amounts of esters and other secondary flavour and aroma products,
and the
result is often a beer with slightly "fruity" compounds resembling those found
in fruits such
as apple, pear, pineapple, banana, plum, cherry, or prune.
Contemplated enriched Ale beers may be based on, or correspond to known (non-
enriched) varieties, for example: (a) Brown Ale, a lightly hopped beer, fairly
mildly
flavoured, often with a nutty taste. Brown ales range from dark brown beers
containing
around 3-3.5% alcohol and quite sweet, to red-brown containing 4.5-5% alcohol,
and drier
beers; (b) Pale Ale, also known as "Bitter Ale", a beer made from malt dried
with coke; (c)
India Pale Ale (IPA), a Pale Ale containing extra hops, a beer appreciated for
its light and
refreshing character; (d) Golden Ale, similar to pale ale but paler, having
from 3.5% to
5.3% alcohol; (e) Scotch Ale, a malty, strong ale, amber-to-dark red in color.
The malt may
be slightly caramelized to impart toffee notes; (f) Barley wine, range from
10% to 12%
alcohol, optionally stored for long periods of time, e.g., about 18 to 24
months. Barley wine
may taste like massive sweet malt and ripe fruit of pear, orange and lemon, or
like darker
fruits, chocolate and coffee if darker malts are used; (g) Mild Ale, or unaged
ale, having
dark brown color and low strength, typically between 3.0 and 3.5% alcohol; (h)
Burton
Ale, a strong, dark, somewhat sweet ale; (i) Old ale, a malty, medium-strong
dark beer
(generally above 5% alcohol), may be treated to resemble the traditional
English old ales;
(j) Belgian Ale, ale high in alcoholic content but relatively light in body
due to the
substitution of part of the grist for sucrose, which provides an alcohol boost
without adding
unfermentable material to the finished product. This process often makes a
beer more
digestible; and (k) Cask Ale, or cask-conditioned beer, an unfiltered and
unpasteurized
beer, which is conditioned (including secondary fermentation) and is served
from
a cask without additional nitrogen or carbon dioxide pressure;
27
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(ii) Porter or Stout. Porter is a dark style of beer made from brown (roasted)
malt
or roasted barley, hops, water and yeast;
(iii) Lager. Lager (from German: storeroom or warehouse) a beer that
is conditioned at low temperatures. It may be pale, golden, amber, or dark.
Lager beer uses
a process of cool fermentation, followed by maturation in cold storage.
Specific yeast
(Saccharomyces pastorianus) is used for brewing Lager.
Contemplated enriched lager beers may be based on, or correspond to known (non-
enriched) varieties, for example: (a) Pale Lager, such as any one of the
common lager beers
in worldwide production, for example, Pilsner beer. The flavor of these
lighter lagers is
usually mild, and it is preferably served refrigerated. Pale lager is a very
pale to golden-
colored lager with a well attenuated body and noble hop bitterness; (b) Vienna
Lager, a
reddish-brown or copper-colored beer with medium body and slight malt
sweetness. The
malt aroma and flavor may have a toasted character; (c) Dark lager, typically
ranging in
color from amber to dark reddish brown and even black such as a Schwarzbier
having a
chocolate or liquorice-like flavour similar to stout. Alcohol concentrations
of 4.5% to
6% by volume; and (d) Bock, a sweet, relatively strong (6.3%-7.2% alcohol by
volume)
lager. This beer is clear, ranging in color from light copper to brown, with a
bountiful and
persistent off-white head.
(iv) Wheat beer. Wheat beer is a beer, usually top-fermented, which is brewed
with
a large proportion of wheat relative to the amount of malted barley.
Contemplated enriched wheat beers may be based on, or correspond to known (non-
enriched) varieties, for example: (a) a German style beer such as WeiBbier
(German ¨
"white beer"), based on the German tradition of mixing at least 50% wheat to
barley malt
to make a light colored top-fermenting beer; and (b) a Belgian style beer such
as Witbier,
based on the Belgian tradition of using flavorings such as coriander and
orange peel.
Belgian style white beers are often made with raw unmalted wheat, as opposed
to the
malted wheat used in other varieties.
In some embodiments, an enriched beer is provided, comprising one or more
dopamine precursors and, optionally, one or more psychostimulant substances as
described
herein in an amount that imparts to the beer palatability and/or positive
psychotropic effects
as defined herein and/or positive psychoactive effects as described herein,
and/or pleasure
28
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
of drinking, at least as those provided by a corresponding non-enriched and/or
any known
beer containing 3.8-10% alcohol by volume.
In certain embodiments, the enriched beer provided herein affords positive
psychoactive effects such as euphoric and joyful feeling, which exceed the
effects exerted
by a corresponding non-enriched beer containing 3.8-10% alcohol by volume,
while
substantially minimizing intoxication effects.
In the enriched beer described herein, the amount of dopamine precursor, for
example, tyrosine, is within a range of from about 0.10 mg/ml to 5.0 mg/ml,
for example,
from about 0.10 mg/ml to about 0.20 mg/ml, from about 0.10 mg/ml to about 0.30
mg/ml,
from about 0.25 mg/ml to about 0.45 mg/ml, from about 0.30 mg/ml to about 0.50
mg/ml,
from about 0.30 mg/ml to about 0.60 mg/ml, from about 0.45 mg/ml to about 0.65
mg/ml,
from about 0.50 mg/ml to about 0.70 mg/ml, from about 0.50 mg/ml to about 0.80
mg/ml,
from about 0.60 mg/ml to about 0.90 mg/ml, from about 0.80 mg/ml to about 1.00
mg/ml,
from about 0.90 mg/ml to about 1.10 mg/ml, from about 0.95 mg/ml to about 1.25
mg/ml,
from about 1.00 mg/ml to about 1.30 mg/ml, from about 1.20 mg/ml to about 1.50
mg/ml,
from about 1.45 mg/ml to about 1.75 mg/ml, from about 1.75 mg/ml to about 2.10
mg/ml,
from about 2.00 mg/ml to about 2.50 mg/ml, from about 2.45 mg/ml to about 3.00
mg/ml,
from about 2.50 mg/ml to about 3.50 mg/ml, from about 3.00 mg/ml to about 4.00
mg/ml,
from about 3.75 mg/ml to about 4.50 mg/ml, or from about 4.35 mg/ml to about
5.00
mg/ml, including any subranges and any intermediate values therebetween.
In exemplary embodiment, the enriched beer provided herein comprises from
about
0.1 mg/ml to about 0.45 mg/ml of tyrosine.
When the enriched beer described herein comprises a psychostimulant substance,
the amount of the psychostimulant substance, for example, caffeine, may be
within a range
selected from 0.01 mg/ml to 0.04 mg/ml, 0.02 mg/ml to 0.05 mg/ml, 0.05 mg/ml
to 0.08
mg/ml, 0.05 to 0.09 mg/ml, 0.05 to 0.10 mg/ml, 0.08 to 0.10 mg/ml, 0.08 to
0.12 mg/ml,
0.09 to 0.15 mg/ml, 0.10 to 0.15 mg/ml, 0.12 to 0.18 mg/ml, 0.12 to 0.20
mg/ml, 0.15 to
0.25 mg/ml, 0.20 to 0.25 mg/ml, 0.25 to 0.45 mg/ml, 0.25 to 0.50 mg/ml, 0.45
to 0.60
mg/ml, 0.50 to 0.75 mg/ml, 0.65 to 0.85 mg/ml, 0.85 to 0.95 mg/ml, 0.95 to
1.00 mg/ml,
0.95 to 1.30 mg/ml, 1.00 to 1.30 mg/ml, 1.00 to 1.50 mg/ml, 1.25 to 1.75
mg/ml, 1.50 to
2.00 mg/ml, 2.00 to 3.00 mg/ml, 3.00 to 5.00 mg/ml, 3.50 to 5.00 mg/ml, 4.50
to 6.00
29
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
mg/ml, or 6.00 to 9.00 mg/ml, including any subranges and any intermediate
values
therebetween.
In certain embodiment, the enriched beer herein comprises from about 0.01
mg/ml
to about 0.9 mg/ml (or 10 mg/L to about 900 mg/L) of caffeine.
In an exemplary embodiment, an enriched beer is provided, comprising a lager
beer,
about 0.1 mg/ml to about 0.6 mg/ml of tyrosine and about 0.01 mg/ml to about
0.75 mg/ml
caffeine.
In some embodiments, the base liquid of the enriched alcoholic beverages
described
herein is wine. The wine may have an alcohol content of 10-14%. The term
"wine" as used
herein and in the art includes the fermented juice of grapes, made in many
varieties, such
as red, white, sweet, dry, still, and sparkling. Exemplary wine beverages
include, but are
not limited to, dry red or white wine; semi-dray red or white wine; rosé wine;
dessert wine
such as Muscato wine; fruit wine; fortified wine such as Marsala, Port,
Madeira, Sherry,
vinsanto, and vermouth; sparkling wine such as Champagne, sangria, table wine.
In some embodiments, the wine is a "reduced alcohol wine", namely a wine as
defined herein comprising up to 8% alcohol, for example, up to 7%, up to 6%,
up to 5%,
up to 4.5%, up to 4%, up to 3.5%, up to 3%, up to 1%, up to 0.5%, up to 0.1%,
up to 0.05%,
or the wine may be devoid of alcohol.
In some embodiments, an enriched wine is contemplated, comprising a dopamine
precursor and, optionally, a psychostimulant substance as described herein in
an amount
that imparts to the wine palatability and/or positive psychotropic effects as
defined herein
and/or positive psychoactive effects as defined herein, and/or pleasure of
drinking, at least
as those provided by a corresponding non-enriched or any known wine containing
10-14%
alcohol by volume.
In certain embodiments, the enriched wine contemplated herein affords positive
psychoactive effects such as euphoric and joyful feeling, which exceed the
effects exerted
by a corresponding non-enriched wine containing 7.5-14% alcohol by volume,
while
substantially minimizing intoxication effects.
In a contemplated enriched wine, the amount of dopamine precursor, for
example,
tyrosine, is within a range of from about 0.10 mg/ml to 5.0 mg/ml, for
example, from about
0.10 to about 0.30 mg/ml, from about 0.25 to about 0.45 mg/ml, from about 0.30
to about
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
0.50 mg/ml, from about 0.30 to about 0.60 mg/ml, from about 0.35 to about 0.65
mg/ml,
from about 0.45 to about 0.65 mg/ml, from about 0.50 to about 0.70 mg/ml, from
about
0.50 to about 0.80 mg/ml, from about 0.60 to about 0.90 mg/ml, from about 0.80
to about
0.95 mg/ml, from about 0.80 to about 1.00 mg/ml, from about 0.90 to about 1.10
mg/ml,
from about 0.95 to about 1.25 mg/ml, from about 1.00 to about 1.30 mg/ml, from
about
1.10 to about 1.50 mg/ml, from about 1.50 to about 1.80 mg/ml, from about 1.55
to about
1.95 mg/ml, from about 1.70 to about 2.00 mg/ml, from about 1.95 to about 2.50
mg/ml,
from about 2.55 to about 2.95 mg/ml, from about 2.80 to about 3.50 mg/ml, from
about
3.50 to about 4.00 mg/ml, from about 3.80 to about 4.50 mg/ml, or from about
4.50 to
about 5.00 mg/ml, including any subranges and any intermediate values
therebetween.
In certain embodiment, the enriched wine contemplated herein comprises from
about 0.1 mg/ml to about 1.80 mg/ml of tyrosine.
When the enriched wine described herein comprises a dopamine supplement, the
amount of dopamine supplement, for example, caffeine, may be within a range
selected
from 0.01 mg/ml to 0.04 mg/ml, 0.02 to 0.05 mg/ml, 0.05 to 0.10 mg/ml, 0.08 to
0.10
mg/ml, 0.08 to 0.12 mg/ml, 0.09 to 0.15 mg/ml, 0.10 to 0.15 mg/ml, 0.12 to
0.18 mg/ml,
0.12 to 0.20 mg/ml, 0.15 to 0.25 mg/ml, 0.20 to 0.25 mg/ml, 0.25 to 0.45
mg/ml, 0.25 to
0.50 mg/ml, 0.45 to 0.60 mg/ml, 0.50 to 0.75 mg/ml, 0.65 to 0.85 mg/ml, 0.85
to 0.95
mg/ml, 0.95 to 1.00 mg/ml, 0.95 to 1.30 mg/ml, 1.00 to 1.30 mg/ml, 1.00 to
1.50 mg/ml,
1.25 to 1.75 mg/ml, or 1.50 to 2.00 mg/ml, including any subranges and any
intermediate
values therebetween.
In exemplary embodiments, the enriched wine contemplated herein comprises from
about 0.01 mg/ml to about 0.75 mg/ml (or 10 mg/L to about 750 mg/L) caffeine.
The term "spirit" as used herein and in the art refers to a distilled alcohol
beverage
obtained, for example, by distilling starchy material, and includes, but not
limited to,
variety of raw grain alcohols, brandies, liquors, saki, Ouzo, arrack, rum,
vodka, tequila,
schnapps, whiskey, gin, cordial, Cachaca, absinthe, baijiu, eau de vie, soju,
aguardiente,
palinka, fernet and slivovitz.
In some embodiments, the spirit is a "reduced alcohol spirit", namely a spirit
as
defined herein comprising up to 80% alcohol, for example, up to 60%, up to
50%, up to
45%, up to 40%, up to 35%, up to 30%, up to 25%, up to 20%, up to 15%, up to
10%, up
31
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
to 8%, up to 7%, up to 6%, up to 5%, up to 4%, up to 3.5%, up to 3%, up to 2%,
up to 1%,
up to 0. 5%, or the spirit may be devoid of alcohol.
In some embodiments, an enriched spirit is contemplated, comprising one or
more
dopamine precursors and, optionally, one or more psychostimulant supplements
as
described herein in an amount that imparts to the spirit palatability and/or
positive
psychotropic effects as defined herein and/or positive psychoactive effects as
described
herein, and/or pleasure of drinking, at least as those provided by any known
corresponding
non-enriched spirit containing 50-98% alcohol by volume.
In certain embodiments, the enriched spirit contemplated herein affords
positive
psychoactive effects such as euphoric and joyful feeling, which exceed the
effects exerted
by a corresponding non-enriched spirit containing 50-98% alcohol by volume,
while
substantially minimizing intoxication effects.
In the enriched spirit described herein, the amount of dopamine precursor, for
example, tyrosine, is within a range of from about 0.10 mg/ml to 5.0 mg/ml,
for example,
from about 0.10 to about 0.30 mg/ml, from about 0.25 to about 0.45 mg/ml, from
about
0.30 to about 0.50 mg/ml, from about 0.30 to about 0.60 mg/ml, from about 0.35
to about
0.65 mg/ml, from about 0.45 to about 0.65 mg/ml, from about 0.50 to about 0.70
mg/ml,
from about 0.50 to about 0.80 mg/ml, from about 0.60 to about 0.90 mg/ml, from
about
0.80 to about 0.95 mg/ml, from about 0.80 to about 1.00 mg/ml, from about 0.90
to about
1.10 mg/ml, from about 0.95 to about 1.25 mg/ml, from about 1.00 to about 1.30
mg/ml,
from about 1.10 to about 1.50 mg/ml, from about 1.50 to about 1.80 mg/ml, from
about
1.55 to about 1.95 mg/ml, from about 1.70 to about 2.00 mg/ml, from about 1.95
to about
2.50 mg/ml, from about 2.55 to about 2.95 mg/ml, from about 2.80 to about 3.50
mg/ml,
from about 3.50 to about 4.00 mg/ml, from about 3.80 to about 4.50 mg/ml, or
from about
4.50 to about 5.00 mg/ml, including any subranges and any intermediate values
therebetween.
In exemplary embodiments, the enriched spirit contemplated herein comprises
from
about 0.1 mg/ml to about 2.5 mg/ml of tyrosine.
When the enriched spirit described herein comprises a psychostimulant
supplement, the amount of psychostimulant supplement, for example, caffeine,
may be
within a range selected from 0.01 mg/ml to 0.04 mg/ml, 0.02 to 0.05 mg/ml,
0.05 to 0.10
32
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
mg/ml, 0.08 to 0.10 mg/ml, 0.08 to 0.12 mg/ml, 0.09 to 0.15 mg/ml, 0.10 to
0.15 mg/ml
0.10 to 0.17 mg/ml, 0.12 to 0.18 mg/ml, 0.12 to 0.20 mg/ml, 0.15 to 0.25
mg/ml, 0.20 to
0.25 mg/ml, 0.23 to 0.35 mg/ml, 0.25 to 0.45 mg/ml, 0.25 to 0.50 mg/ml, 0.45
to 0.60
mg/ml, 0.50 to 0.75 mg/ml, 0.65 to 0.85 mg/ml, 0.70 to 0.95 mg/ml, 0.95 to
1.00 mg/ml,
0.95 to 1.30 mg/ml, 1.00 to 1.30 mg/ml, 1.00 to 1.50 mg/ml, 1.25 to 1.75
mg/ml, 1.50 to
2.00 mg/ml, 1.60 to 2.30 mg/ml, or 2.30 to 2.60 mg/ml, including any subranges
and any
intermediate values therebetween.
In exemplary embodiments, the enriched spirit contemplated herein comprises
from
about 0.01 mg/ml to about 0.75 mg/ml (or 10 mg/L to about 750 mg/L) caffeine.
Other known alcoholic beverages which can be made enriched alcoholic beverages
in accordance with embodiments described herein, include, but are not limited
to, Desi
daru, made by fermenting molasses or high sugar containing fruits; Huangjiu
(Chinese,
made from rice, millet, or wheat using a special starter culture of yeast,
mold, and bacteria);
Icariine Liquor; Kasiri (made from cassava); Kilju (Finnish, made from sugar);
Kumis (central asia, traditionally made from horse milk but now primarily cow
milk);
Mead (made from honey); Nihamanchi (South America) a.k.a. nijimanche (Ecuador
and
Peru) (made from cassava); Palm wine (made from the sap of various palm
trees); Parakari
(made from cassava); Pulque (originally made by the natives of Mexico, made
from the
sap of the maguey plant); Sakura (made from cassava); Sake (made from rice);
Sonti;
Tepache; Tiswin (made from corn or saguaro, a large cactus); and Tonto.
Herein throughout, whenever a percentage (%) is indicated, volume % of the
total
volume of the beverage is meant, unless otherwise indicated.
Alcopop beverages, also termed herein and in the art "coolers" or "spirit
coolers",
are flavored alcoholic beverages or flavored malt beverages based on fruit
juice or nectar,
and/or a variety of naturally and/or artificially flavored syrups. Exemplary
alcopop
beverages include, but are not limited to (i) a malt beverage, designate
herein "a beer
cooler", containing a malt base or beer and at least 5% by volume of added
natural or
artificial blending material, such as fruit juice, flavors, flavorings,
colorings, and,
optionally, preservatives; (ii) a wine cooler which is a beverage containing
wine and more
than 15% by volume of added natural or artificial blending material, such as
fruit juices,
flavors, flavorings, adjuncts, water (plain, carbonated, or sparkling),
colorings, and,
33
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
optionally, preservatives; and (iii) a beverage designated herein "a spirit
cooler",
containing distilled alcohol, and added natural or artificial blending
material, such as fruit
juices, flavors, flavorings, colorings, and, optionally, preservatives.
Alcopop brands are numerous and their alcoholic base vary greatly. Most
alcopop
beverages contain 3.8-7% alcohol by volume, and some may even contain as much
as
12.5% alcohol by volume. Some notable brands include, but are not limited to,
Smirnoff
Ice, Mike's Hard Lemonade, Bacardi Breezer, Skyy Blue, Jack Daniel's Hard
Cola, WKD
Original Vodka, Six Degrees and MG Spirits.
In some embodiments, an enriched cider and/or enriched alcopop beverage is
contemplated, comprising one or more dopamine precursors and, optionally, one
or more
psychostimulant supplements as described herein in an amount that imparts to
the beer
palatability and/or positive psychotropic effects as defined herein and/or
positive
psychoactive effects as described herein, and/or pleasure of drinking, at
least as those
provided by a corresponding non-enriched or any known alcopop or cider
containing 3.8-
10% alcohol by volume.
In certain embodiments, the enriched alcopop or enriched cider contemplated
herein affords positive psychoactive effects such as euphoric and joyful
feeling, which
exceed the effects exerted by a corresponding non-enriched alcopop or non-
enriched cider
containing 3.8-10% alcohol by volume, while substantially minimizing
intoxication
effects.
In the enriched alcopop described herein, the amount of dopamine precursor,
for
example, tyrosine, is within a range of from about 0.10 mg/ml to 5.0 mg/ml,
for example,
from about 0.10 mg/ml to about 0.20 mg/ml, from about 0.10 to about 0.30
mg/ml, from
about 0.25 to about 0.45 mg/ml, from about 0.30 to about 0.50 mg/ml, from
about 0.30 to
about 0.60 mg/ml, from about 0.35 to about 0.65 mg/ml, from about 0.45 to
about 0.65
mg/ml, from about 0.45 to about 0.70 mg/ml, from about 0.50 to about 0.70
mg/ml, from
about 0.50 to about 0.80 mg/ml, from about 0.60 to about 0.90 mg/ml, from
about 0.80 to
about 0.95 mg/ml, from about 0.80 to about 1.00 mg/ml, from about 0.90 to
about 1.10
mg/ml, from about 0.95 to about 1.25 mg/ml, from about 1.00 to about 1.30
mg/ml, from
about 1.10 to about 1.30 mg/ml, from about 1.20 to about 1.50 mg/ml, from
about 1.55 to
about 1.75 mg/ml, from about 1.75 to about 2.10 mg/ml, from about 1.95 to
about 2.50
34
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
mg/ml, from about 2.55 to about 2.95 mg/ml, from about 2.80 to about 3.50
mg/ml, from
about 3.50 to about 4.00 mg/ml, from about 3.80 to about 4.50 mg/ml, or from
about 4.50
to about 5.00 mg/ml including any subranges and any intermediate values
therebetween.
In certain embodiment, the enriched alcopop contemplated herein comprises from
about 0.1 mg/ml to about 0.45 mg/ml of tyrosine.
When the enriched alcopop described herein comprises a psychostimulant
supplement, the amount of psychostimulant supplement, for example, caffeine,
may be
within a range selected from 0.01 mg/ml to 0.04 mg/ml, 0.02 to 0.05 mg/ml,
0.05 to 0.10
mg/ml, 0.08 to 0.10 mg/ml, 0.08 to 0.12 mg/ml, 0.09 to 0.15 mg/ml, 0.10 to
0.15 mg/ml,
0.12 to 0.18 mg/ml, 0.12 to 0.20 mg/ml, 0.15 to 0.25 mg/ml, 0.20 to 0.25
mg/ml, 0.25 to
0.45 mg/ml, 0.25 to 0.50 mg/ml, 0.45 to 0.60 mg/ml, 0.50 to 0.75 mg/ml, 0.65
to 0.85
mg/ml, 0.85 to 0.95 mg/ml, 0.95 to 1.00 mg/ml, 0.95 to 1.30 mg/ml, 1.00 to
1.30 mg/ml,
1.00 to 1.50 mg/ml, 1.25 to 1.75 mg/ml, or 1.50 to 2.00 mg/ml, including any
subranges
and any intermediate values therebetween.
In exemplary embodiments, the enriched alcopop contemplated herein comprises
from about 0.01 mg/ml to about 0.75 mg/ml (or 10 mg/L to about 750 mg/L)
caffeine.
Herein throughout, whenever a percentage (%) is indicated, % volume of the
total
volume (% v/v) of the beverage is meant, unless otherwise indicated.
In some of any one of the embodiments of the present invention, optionally or
additionally, the base material of the enriched alcoholic food product, for
example, base
liquid or base alcoholic liquid, is formulated to include additives, such as
flavoring agents,
colorants, odoriferous agents, enzymes, CO2 and/or other additives such as
viscosity
modifying agents, foaming agents, antifoaming agents, and preservatives that
account for
the taste and texture of e.g., wine or beer or spirit, such that the enriched
alcoholic product
will contain at least part or all the ingredients used to form the
corresponding non-enriched
alcoholic product. Preferably, additives used in the enriched alcohol products
described
herein are FDA-approved, and/or edible. In some embodiments, the additives are
selected
as soluble in the base material, e.g. base alcoholic beverage or base liquid.
The phrases "flavoring agent" and "odoriferous agent", as used herein,
describe a
class of substances which are added to edible products in order to induce a
certain flavor
or smell in the product, respectively, and are commonly referred to also as
"flavorants".
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Flavorants, also termed herein "taste-improving additives", can be synthetic
or natural
extracts, which are extracted from a source substance. Typical flavorants are
specific and
often complex mixtures of singular naturally occurring or synthetic flavor
compounds
combined together to either imitate or enhance a natural flavor. Many
flavorants are esters,
which can be characterized by a typical flavor, such as diacetyl which gives a
buttery
flavor, isoamyl acetate that is perceived as banana, cinnamic aldehyde which
is the basis
for the typical flavor of cinnamon, ethyl propionate is perceived as fruity,
limonene is
perceived as orange, ethyl-(E, Z)-2,4-decadienoate is perceived as pear, allyl
hexanoate is
perceived as pineapple, ethyl maltol, is perceived as sugar or cotton candy,
methyl
salicylate is known as the wintergreen flavor, and benzaldehyde is perceived
as bitter
almond. Further synthetic flavorant are exemplified by amaretto, cola and ice
cream flavors
Flavoring agent of a natural source can be, for example, an extract of a
fruit, a
vegetable, a herb or of any other edible substance, a fruit juice or a
vegetable juice, or any
combination thereof. Non-limiting examples of fruit flavorants include elder,
grape,
orange, ginger, red apple, anise, or lemon grass. These additives are added in
addition to
or instead of those found in the alcoholic beverage, if indeed present
therein.
The term "colorant", as used herein, refers to any natural or synthetic
coloring
substance, and describes any substance that is added to food or drink in order
to alter its
color. Exemplary usable colorants include, but are not limited to, synthetic
colorants such
as FD&C Blue No. 1 - Brilliant Blue FCF (E133), FD&C Blue No. 2 ¨ Indigotine
(E132),
FD&C Green No. 3 - Fast Green FCF (E143), FD&C Red No. 40 - Allura Red AC
(E129),
FD&C Red No. 3 ¨ erythrosine (E127), FD&C Yellow No. 5 ¨ tartrazine (E102),
and
FD&C Yellow No. 6 - Sunset Yellow FCF (E110), and natural food colorants such
as
carmine (E120), enocianin (E163), black carrot (E163), paprika (E160c),
annatto (E160b),
beta carotene (E160a), lutein (E161b), riboflavin (E101), curcumin (E100),
copper
chlorophyllin (E141), chlorophyll (E140), caramel (E150), and extracts of
foodstuffs such
as elderberry, aronia, grape, beetroot, carrot, turmeric (tumeric) root,
spinach, stinging
nettle and burnt sugar (caramelized sugar).
The term "preservative", as used herein, describes a synthetic or natural
additive
substance that is added to edible products in order to prevent or retard
chemical and
biochemical decomposition of the product by oxygen, moisture and/or microbes.
36
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Exemplary anti-microbial preservatives include, but are not limited to,
calcium propionate,
sodium nitrate, sodium nitrite, sulfites (sulfur dioxide, sodium bisulfite,
potassium
hydrogen sulfite, etc.), disodium EDTA, sodium benzoate, potassium sorbate.
Natural
substances that retard microorganisms growth include lactic acid, salt, sugar
and vinegar.
Exemplary antioxidant preservatives include, but are not limited to, butylated
hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). Natural antioxidants
include, but are not limited to, herbal extracts such as rosemary and oregano,
and vitamins
such as Vitamin E and Vitamin C (ascorbic acid).
The phrase "foaming agent", as used herein, describes an edible surfactant,
which
when present in small amounts, facilitates the formation of a foam, or
enhances its colloidal
stability by inhibiting the coalescence of bubbles. Exemplary foaming agents
include,
without limitation, sodium laureth/lauryl sulfate (SLS), sodium lauryl ether
sulfate (SLES)
and ammonium lauryl sulfate (ALS).
The phrase "antifoaming agent", as used herein, describes an edible substance
that
inhibits the formation of foam and curbs effusion or effervescence in edible
products. An
exemplary antifoaming agent is polydimethylsiloxane.
The phrases "viscosity modifying agent" or "thickener" as used herein are
interchangeable and describe agents that enable to control the viscosity of
the enriched
alcoholic products described herein. Exemplary thickeners include, but are not
limited to,
starch-based thickeners such as maltodextrin and gum-based thickeners such as
xanthan or
cellulose gum.
The enriched alcoholic products described herein may be contained in any of
the
known containers applied for alcoholic products in general. For example, when
the
enriched alcoholic product is a beverage, for example a beer, it may be
contained and
marketed in a 330 ml, 500 ml, 750 ml and 1-liter bottle or tin, or in a
barrel. The stability
of the enriched alcoholic product obtained according to any of the embodiments
described
herein is preferably more than 365 days at room temperature, and it may be
stored for up
to 999 days at 10 C.
In an aspect of some embodiments of the present invention there is provided a
process for the preparation of an enriched alcoholic beverage. The process
comprises
mixing a base liquid as defined herein with an amount of one or more
neurotransmitter
37
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
precursors and/or one or more neurotransmitter precursors as described herein.
In some
embodiments, the process further comprises the addition of one or more
psychostimulant
supplements as described herein. In some embodiments, the base liquid is an
alcoholic
beverage such as beer, wine, spirit, cider or alcopop.
In some embodiments, the base liquid is a non-alcoholic beverage (e.g, juice,
water
and the like), and one or more neurotransmitter precursors and/or one or more
neurotransmitter precursors and, optionally one or more psychostimulant
supplements may
be added to the non-alcoholic base beverage together with a desired amount of
alcohol.
In some embodiments, the enriched alcoholic beverage, for example beer, is
prepared by brewing the beer together with neurotransmitter precursor(s) and
the
psychostimulant supplement(s). Likewise, wine and spirit may be fermented or
distilled,
respectively, in processes that are adjusted to includes steps of addition of
neurotransmitter
precursor(s) and psychostimulant supplement(s), as long as the fermentation,
distillation
or brewing processes maintain the neurotransmitter precursor(s) and the
psychostimulant
supplement(s) intact and bioavailable, and further provided that the
palatability, texture
and appearance of the beverage in not substantially affected by including
neurotransmitter
precursor(s) and/or the psychostimulant supplement(s) in the process of
preparation
thereof.
In exemplary embodiments, the process described herein is for the preparation
of
enriched beers comprising one or more dopamine precursors and, optionally
further
comprising one or more psychostimulant supplements in the amounts described
herein.
In exemplar embodiments, in the process provided herein, tyrosine and caffeine
are
provided to a base alcoholic beer. In alternative embodiments, an enriched
beer is brewed
together with tyrosine and caffeine in the brewery.
It is to be understood that the invention as described and discussed in the
foregoing
and in following sections of the description is not necessarily limited in its
application to
the details set forth in the present description.
Whenever a numerical range is indicated herein, it is meant to include any
cited
numeral (fractional or integral) within the indicated range. The phrases
"ranging/ranges
between" a first indicate number and a second indicate number and
"ranging/ranges from"
38
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
a first indicate number "to" a second indicate number are used herein
interchangeably and
are meant to include the first and second indicated numbers and all the
fractional and
integral numerals therebetween.
The dimensions and values disclosed herein are not to be understood as being
strictly limited to the exact numerical values recited. Instead, unless
otherwise specified,
each such dimension is intended to mean both the recited value and a
functionally
equivalent range surrounding that value. For example, a dimension disclosed as
"10 pm"
is intended to mean "about 10 pm".
The term "about" as used herein means within an acceptable error range for a
particular value as determined by one of ordinary skill in the art, which will
depend in part
on how the value is measured or determined, i.e., the limitations of the
measurement
system. For example, "about" can mean a range of up to 10%, more preferably up
to 5%,
and still more preferably up to 1% of a given value.
The terms "comprises", "comprising", "includes", "including", "having" and
their
conjugates mean "including but not limited to".
The term "consisting of' means "including and limited to".
The term "consisting essentially of" means that the compositions, for example,
enriched alcoholic beverages, may include additional ingredients but only if
the additional
ingredients do not materially alter the basic and novel characteristics of the
claimed
composition.
As used herein, the singular form "a", "an" and "the" include plural
references
unless the context clearly dictates otherwise. For example, the term "a
compound" or "at
least one compound" may include a plurality of compounds, including mixtures
thereof.
It is appreciated that certain features of the invention, which are, for
clarity,
described in the context of separate embodiments, may also be provided in
combination in
a single embodiment. Conversely, various features of the invention, which are,
for brevity,
described in the context of a single embodiment, may also be provided
separately or in any
suitable subcombination or as suitable in any other described embodiment of
the invention.
Certain features described in the context of various embodiments are not to be
considered
essential features of those embodiments, unless the embodiment is inoperative
without
those elements.
39
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Various embodiments and aspects of the present invention as delineated
hereinabove and as claimed in the claims section below find experimental
support in the
following examples.
EXAMPLES
EXAMPLE 1
Preparation of beer enriched with tyrosine and caffeine
Beer enriched with tyrosine and caffeine was prepared using a protocol
comprising
the following steps:
(i) grinding barley;
(ii) immersing the grinded barley in water at a temperature of 50-75 C for
about an
hour;
(iii) adding caffeine;
(iv) transferring the mixture of grinded barley and caffeine to a boiler;
(v) adding hops to the mixture in the boiler, and boiling the mixture for
about an
hour;
(vi) transferring the boiling mass (herein referred to as the "must") into a
fermentation tank via a heat exchanger apparatus that cools the must form 100
C to about
20 C;
(v) adding yeasts to the cooled must;
(vi) fermenting the must for a period of 14 to 16 days so as to obtain a beer;
(vii) transferring the fermented mass into a second tank (herein also termed
"intermediate tank");
(viii) adding tyrosine and, optionally, glucose and to the fermented beer; and
(ix) transferring the beer to bottles, cans or barrels and storing for a
second
fermentation for a period of 12-40 days at 18 C.
The enriched beer was unfiltered and contained 5.5% alcohol by volume, and 40
mg tyrosine and 35 mg caffeine, per 100 ml.
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
EXAMPLE 2
Beer enriched with tyrosine and caffeine
A further recipe for brewing beer enriched with tyrosine and caffeine
comprises the
following steps:
(i) milling malted barley;
(ii) mashing: transferring milled malted barley into mash tun, adding water
and
heating to a temperature of from about 50 C to about 75 C for about 1 - 2
hour;
(iii) lautering: separating the wort (the malty liquid that was extracted
during
mashing) from the grains;
(iv) adding tyrosine (from about 100 mg/L to about 5000 mg/L);
(v) boiling the wort;
(vi) adding hops and boiling the mixture for about 45 - 90 minutes;
(vii) separating hopped wort from solid particles;
(viii) cooling the wort to fermentation temperature (about 4 ¨ 25 C) and
aerating
it;
(ix) adding brewer's yeasts and fermenting the wort for several weeks;
(x) conditioning/maturing: separating fermented beer from dead yeasts and
other
debris and transferring it into a conditioning tank for a period of several
weeks to several
months;
(xi) filtering the beer;
(xii) adding caffeine (from about 10 mg/L to about 700 mg/L);
(xiii) heating the beer to 70 C for pasteurization (elimination of harmful
bacteria)
and to fully dissolve added tyrosine and caffeine; and
(xiv) packaging the enriched beer (i.e., bottling, canning and/or transferring
to a
barrel), and cooling for storage.
EXAMPLE 3
Akopop ("hard lemonade") enriched with tyrosine and caffeine
Hard lemonade, an alcopop, enriched with tyrosine and caffeine is prepared
according to the following steps:
(i) grinding mint leaves with brown sugar;
41
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(ii) adding boiling water;
(iii) adding tyrosine (from about 100 mg/L to about 5000 mg/L), and stirring
the
tyrosine-containing mixture;
(iv) adding the following ingredients to the above mixture: water (at room
temperature), a spirit with at least 40% alcohol (e.g., vodka), and freshly
squeezed lemon
juice with pulp, in a ratio mixture:water:vodka:lemon juice of about 1:5:4:2;
(v) adding caffeine (from about 10 mg/L to about 700 mg/L); and
(vi) bottling and/or canning the enriched alcopop and cooling for storage.
EXAMPLE 4
White wine enriched with tyrosine and caffeine
White wine enriched with tyrosine and caffeine is prepared according to the
following steps:
(i) crushing, pressing and extracting the grape juice (wort) of white-flesh
grapes (so
as to separate it from skins, seeds and other solids);
(ii) clearing the wort to remove lees, for example, by settling or by other
methods;
(iii) adding tyrosine (from about 100 mg/L to about 5000 mg/L);
(iv) optionally, adding wine yeasts to the wort in addition to the existing
natural
yeasts;
(v) fermenting the wort in fermentation tanks for several weeks at a
temperature of
12 ¨ 37 C;
(vi) eliminating fermentation, if desired.
(vii) clearing and refining: separating the fermented wine from dead yeasts
and
other debris, for example, by filtration or by other methods;
(viii) adding caffeine (from about 10 mg/L to about 700 mg/L; and
(ix) bottling the enriched wine.
EXAMPLE 5
Red wine enriched with tyrosine and caffeine
Red wine enriched with tyrosine and caffeine is prepared according to the
following
steps:
42
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(i) destemming and crushing grapes to create a must (i.e., a mixture of
grapes, skins,
juice and seeds);
(ii) settling the must for pre-fermentation maceration at a temperature of
about 10
C for a period of 1 to 4 days;
(iii) adding tyrosine (from about 100 mg/L to about 5000 mg/L);
(iv) optionally, adding wine yeasts to the wort in addition to the existing
natural
yeasts;
(v) fermenting the must in fermentation tanks for several weeks at a
temperature of
12 ¨ 37 C. During fermentation, the contact between skins and liquid phase
can be
maximized by a desired mixing method;
(vi) extracting the juice from the must by pressing and separating it from
remaining
solids;
(vii) allowing for malolactic fermentation;
(viii) racking: decanting off lees (dead yeasts and other solids) and
providing sulfur
dioxide preservative to avoid oxidation and bacterial spoilage;
(ix) aging/maturing the wine for a desired period;
(x) clearing and refining, for example, by filtration or by other methods;
(xi) adding caffeine (from about 10 mg/L to about 750 mg/L; and
(xii) bottling the enriched wine.
EXAMPLE 6
Cider enriched with tyrosine and caffeine
"Hard cider" enriched with tyrosine and caffeine is prepared according to the
following steps:
(i) crushing and pressing apples to acquire must (apple juice) from pomace
(mixture
of solid remains of pressed apples, skins, juice and seeds);
cii) adding tyrosine to concentrations of 100 mg/L ¨ 5 gr/L;
(iii) optionally, adding cider yeasts to the must, in addition to existing
natural
yeasts;
(iv) fermenting the must in fermentation tanks for several weeks at a
temperature
of 4 ¨ 16 C;
43
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(v) racking: siphoning the liquor into new vats, separating it from dead
yeasts and
undesirable materials;
(vi) aging/maturing the cider for a desired period;
(vii) adding caffeine to concentrations of 10 mg/L to about 750 mg/L; and
(viii) packaging the enriched cider (i.e., bottling, canning and/or
transferring to a
barrel), and cooling for storage.
EXAMPLE 7
Single Malt whisky enriched with tyrosine and caffeine
Single Malt whisky enriched with tyrosine and caffeine is prepared according
to
the following steps:
(i) milling malted barley;
(ii) mashing: transferring milled malted barley into mash tun, adding hot
water in
three stages and exceeding temperatures (beginning with approx. 60 C, then
approx. 75
C and, finally, approx. 90 C). Wort (the malty liquid that is extracted
during mashing) is
transferred into a washback;
(iii) cooling the wort to fermentation temperature (about 4-25 C);
(iv) adding whisky yeasts;
(v) fermenting the cooled wort for up to several days to receive the "wash";
(vi) distilling the wash twice using stills: first using wash stills to obtain
"low wine",
and a second time using spirit stills to obtain the final "new-make" spirit
(unaged whisky).
During the second distillation, the more volatile compounds which distil off
first
(foreshots), and the final stage where more oily compounds are vaporized, are
both
channeled off so that only the pure center cut is collected;
(vii) optionally, diluting the new-make prior to aging;
(viii) transferring new-make to wooden casks and aging for several years;
(ix) chill filtrating: precipitating and filtering to remove fatty acid
esters;
(x) adding tyrosine (final concentration 100 mg/L ¨ 5 gr/L);
(xi) adding caffeine (final concentrations 10 mg/L to about 750 mg/L); and
(xii) bottling the enriched whisky.
44
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
EXAMPLE 8
Vodka enriched with tyrosine and caffeine
Vodka enriched with tyrosine and caffeine is prepared according to the
following
steps:
(i) mashing desired starchy ingredient (potatoes, milled grains, etc.), adding
water
and boiling;
(ii) cooling the mash to enzyme activity temperatures;
(iii) adding starch-breaking enzymes, such as amylase;
(iv) allowing enzyme activity to break down starch within mash to small
sugars;
(v) adding vodka yeasts;
(vi) fermenting the starch-broken mash for several days in yeast-activity
temperatures (about 4 ¨ 25 C) to obtain the "wash" (i.e., insipid beverage);
(vii) distilling the wash using standard methods to obtain raw spirit of ¨60%
alcohol
by volume (ABV). Separating and discarding products of the first and last
distillation
stages (i.e., first 5% and final 35% of the whole distillation process);
(viii) rectifying the raw spirit to neutral spirit of ¨96% ABV;
(ix) preparing demineralized water solution containing tyrosine (80 - 585
mg/L)
and caffeine (15-670 mg/L), heating to ¨80 C until homogenous, and then
cooling to
ambient temperature;
(x) adding the demineralized water solution to the neutral spirit to reduce
ABV to
¨40%;
(xi) filtering the obtained enriched vodka using standard methods; and
(xii) bottling the enriched vodka.
EXAMPLE 9
Coffee liqueur enriched with tyrosine and caffeine
Coffee liqueur enriched with tyrosine and caffeine is prepared according to
the
following steps:
(i) combining 3 cups of sugar, 2 cups of water and a tablespoon of vanilla
extract
in a saucepan;
(ii) boiling and stiffing for approx. 30 minutes until volume is reduced by
half;
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
(iii) adding 100 - 400 mg tyrosine and about 100 gr instant coffee, stiffing
until
homogenous and allowing the syrup mixture to cool;
(iv) combining the syrup with 750 ml 40% ABV vodka in a closed 1-liter bottle,
and shaking well;
(v) optionally, adding up to 180 mg caffeine;
(vi) settling for 10 days in a cool, dark place;
(vii) Straining/filtering the enriched liqueur; and
(viii) bottling the enriched liqueur.
EXAMPLE 10
Biphasic Alcohol Effects Scale (BAES) study
The stimulant and sedative effects caused by consuming a beer enriched with a
neurotransmitter precursor such as Tyr and, optionally, a psychostimulant
substance such
as caffeine, versus the stimulant and sedative effects exerted by a
corresponding non-
enriched beer was assessed in self-reporting participants using a Biphasic
Alcohol Effects
Scale (BAES)-based questionnaire. The BAES is a reliable and valid systematic
14-item
self-report scale designed to measure stimulant and sedative effects of
alcohol as separate
and distinct constructs. BAES and a brief version thereof (B-BAES) comprising
only 6
items are described, for example, in Rueger and King, 2013 (Alcohol Chn Exp
Res. 37(3):
470-476; and references cited therein).
Seven items comprise the stimulant subscale of the BAES (elated, energized,
excited, stimulated, talkative, up, vigorous), and another seven items
comprise the sedative
subscale (difficulty in concentrating, down, heavy head, inactive, sedated,
slow thoughts,
sluggish). The BAES test demonstrates strong psychometric properties,
including high
internal consistency, reliability and a four-factor structure reflecting the
distinctness of the
stimulant and sedative constructs during both the ascending and descending
limbs of the
breath alcohol concentration (BrAC) curve. With use of a conversion factor,
called the
blood:breath ratio (BBR), the blood alcohol concentration (BAC) can be
estimated from
BrAC. This four-factor structure is invariant to dose, drinking history, and
sex, and
demonstrates robustness to an instructional set that does not disclose the
content of the
alcoholic beverage (see, for example, Rueger et al., 2009, Alcohol Clin Exp
Res. 33:916-
924).
46
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
The BAES study of alcohol effects in accordance with the disclosed study had
multiple assessments in one session. For example, the BAES questionnaire was
administered before alcohol was consumed and then the assessment was repeated
3-4 more
times after consumption to capture rising and declining BrAC limb effects.
In the BAES questionnaire exemplified herein, each participant was presented
with
14 items in alphabetical order, 7 of which describe sensations (feelings,
perception)
associated with stimulant effects (elevated mood (high spirit), energy,
excitement,
stimulated, talkativeness, vigorous and vitality), and 7 items describing
sensations
(feelings, perception) associated with sedative effects (difficulty in
concentrating, down
feeling, heavy head, heavy body, sedative, slow thinking, sluggishness). Each
participant
had to assign, next to each of these 14 items, a number in the range from 0 to
10 indicating
how closely or how well a certain item expresses, corresponds or describes
his/her current
feeling/sensation, where "0" indicates "not at all describing" or
"irrelevant", and "10"
indicates "exactly (or very much) describing".
The numerical indications of the stimulant and sedative effects were averaged
to
obtain two numerical values designated STIM and SED, respectively.
Participants
Healthy nonalcoholic 198 social drinkers participated in the study.
Participants
were recruited from the wider community via advertising placed, for example,
in web sites.
Each participant's eligibility was subject to the following criteria: (i) aged
18-60 years; (ii)
no history of alcohol addiction; (iii) not taking medication having a
stimulative or sedative
action; (iv) moderate to low regular consumption of alcohol.
Participants were randomly supplied with either one of: (i) an alcoholic
beverage,
e.g., beer, enriched with tyrosine and caffeine; or (ii) a corresponding non-
enriched
alcoholic beverage. The study was double-blind, and the participants did not
know whether
they were supplied with alcoholic beverage (i) or (ii). The gender split was
equal across
both groups. All participants were requested to refrain from alcohol
consumption at least
24 hours before the study.
47
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Study design
The study was a 2-sesssion (2 days) study, wherein the second session (day)
was at
least a week apart from the first session. Participants were either given an
enriched (i.e.,
comprising Tyr and caffeine) or non-enriched beer having 5.2% alcohol.
In each session, participants first filled a BAES questionnaire to set up a
baseline
assessment, followed (about 5 minutes later) by the consumption of either
enriched beer
(i) or non-enriched beer (ii). For each participant, the amount of beer
provided was
calculated so as to reach blood alcohol level of 0.35 gr per kg body weight.
For example,
for a participant weighting 75 kg, 26.25 gr of alcohol are required in order
to reach the
predetermined blood alcohol concentration, thus this participant was supplied
with 504.8
ml beer having 5.2% alcohol.
The total amount of alcohol for a participant was divided into 5 equal
portions, and
the participant was requested to consume each portion within 2 minutes
(overall, 10 min
for consuming the whole amount of alcoholic beverage). Immediately after the
last portion
of beverage was fully consumed, time point zero (T=0) was set. Participant
were requested
to fill a BAES questionnaire at T= 30 min, T= 60 mm and at T=120 min.
Answers obtained from all BAES questionnaires were gathered, averaged
(standard
deviation was calculated) to obtain the STIM and SED values, and presented
graphically.
The results are shown in Figures 1A-1B and 2A-2B, and presented in Tables 1
and 2.
Table 1. BAES study for non-enriched (regular) beer
Regular (non-enriched) Beer
STIM SD SED SD
Baseline 3.20 0.76 1.51 0.39
30 min 3.54 0.69 1.90 0.50
60 min 2.49 0.52 2.78 0.53
120 min 2.15 0.45 3.33 0.64
48
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
Table 2. BAES study for beer enriched with tyrosine and caffeine
Enriched Beer
STIM SD SED SD
Baseline 3.08 0.77 1.30 0.40
30 min 5.32 0.83 1.10 0.38
60 min 5.04 0.79 1.07 0.38
120 min 4.05 0.61 1.10 0.35
As seen in Table 1, and Figures 1A and 2A, 30 minutes after the regular (non-
enriched beer) was consumed, participants experienced slight stimulant and
sedative
effects. Sixty minutes (T=60) and 120 minutes after consumption, the sedative
effects
increase while stimulant effects decreased even below baseline levels.
On the other hand, as seen in Table 2, and Figures 1B and 2B, 30 minutes after
the
enriched beer was consumed, significant elevation of stimulant effects was
demonstrated,
along with a slight rise in sedative effects. Sixty minutes (T=60) and 120
minutes after
consumption of the enriched beer, the stimulant effects gradually regress or
decrease, but
they were still higher compared to consumption of non-enriched beer. No
significant
change was seen in the sedative effects, namely, they remained low even after
120 min.
It is shown herein that the beer enriched with Tyr and caffeine significantly
strengthens and prolongs the stimulant and mood elevating effects associated
with alcohol
consumption as compared to a corresponding non-enriched beer, while
significantly
reducing, nearly nulling, the sedative effects, and for much longer time
compared to non-
enriched beer.
Although the invention has been described in conjunction with specific
embodiments thereof, it is evident that many alternatives, modifications and
variations will
be apparent to those skilled in the art. Accordingly, it is intended to
embrace all such
alternatives, modifications and variations that fall within the spirit and
broad scope of the
appended claims.
All publications, patents and patent applications mentioned in this
specification are
herein incorporated in their entirety by reference into the specification, to
the same extent
as if each individual publication, patent or patent application was
specifically and
49
CA 03071959 2020-02-03
WO 2019/038687
PCT/IB2018/056348
individually indicated to be incorporated herein by reference. In addition,
citation or
identification of any reference in this application shall not be construed as
an admission that
such reference is available as prior art to the present invention. To the
extent that section
headings are used, they should not be construed as necessarily limiting.
