Euphoria Research

A. Dopamine and the Mesolimbic Pathway – An Introduction

Dopamine is a neurotransmitter used in the central and peripheral nervous system. In the brain, Dopaminergic neurons – neurons that produce and release Dopamine – are key players in neural pathways monitoring many crucial processes such as motor, mood, memory, sleep, learning and motivation. Unbalanced levels of Dopamine are associated with ADHD and illnesses such as Parkinson’s disease, depression and schizophrenia [1].

Dopamine is released in the Mesolimbic Pathway of the Reward System whenever we experience feelings of pleasure and happiness [2] and has a crucial role in forming these sensations, as well as in mechanisms of addiction and its development.

Neurotransmitter Dopamine must be synthesized within the brain as it is impenetrable to the blood-brain barrier [3]. Its synthesis takes place in the neuronal cytosol and begins with the hydroxylation of the non-essential amino acid L-Tyrosine by the enzyme Tyrosine Hydroxylase to yield L-DOPA. This is the rate-limiting step of the Dopamine synthesis chain of reactions [4]. L-DOPA is then decarboxylated to Dopamine by the enzyme L-DOPA Decarboxylase. Dopamine may be later used as a substrate to synthesize the catecholamine neurotransmitters Norepinephrine and Epinephrine [5].

Neurotransmitter Dopamine has a key role in creating the feeling of elation followed by the consumption of alcohol, as alcohol promotes its release in the Mesolimbic Pathway [6] which is associated with forming pleasant and happy sensations [7].

[1]  Klein M. O. et al. (2019). “Dopamine: Functions, Signaling, and Association with Neurological Diseases”, Cell. Mol. Neurobiol., 39(1), 31-59.
[2] Arias-Carrión O., Pŏppel E. (2007). ” Dopamine, learning, and reward-seeking behavior.”, Acta. Neurobiol. Exp. (Wars), 67(4), 481-8.
[3] Laterra, J. (1999). “Blood-Brain-Cerebrospinal Fluid Barriers.” In G.J. Siegel (Eds.), Basic Neurochemistry (6th ed.), Philadelphia: Lippincott-Raven.
[4] Flatmark T. (2000). “Catecholamine biosynthesis and physiological regulation in neuroendocrine cells.” Acta Physiol. Scand., 168(1), 1-17.
[5] Meiser, J. et al. (2003). “Complexity of dopamine metabolism.” Cell Commun. Signal., 11(1).
[6] Boileau, I. et al. (2003). “Alcohol promotes dopamine release in the human nucleus accumbens.” Synapse, 49(4), 226-31.
[7] Engel, J.A., Jerlhag, E. (2014). “Alcohol: mechanisms along the mesolimbic dopamine system.” Prog. Brain Res., 211, 201-33.

B. Leading Hypothesis

The hypothesis that lead the starting point of our research was that alcohol consumption triggers an immediate, acute and unbalanced secretion of neuronal Dopamine to the synaptic cleft, which then promotes its degradation there so that previously reduced and balanced levels are attained. This upregulated degradation depletes the neuronal Dopamine reserves, reduces overall synaptic Dopamine levels and is expressed by negative symptoms that are experienced during the later stages that follow alcohol consumption: poor mood, heavy feeling and depression –
Considering the above, the derived breakthrough conclusion is that by supporting the natural neuronal synthesis of Dopamine to maintain a steady supply of abundant and available reserves during the consumption of alcohol, we can prevent the negative mood symptoms that are associated with Dopamine-depletion, while enhancing and prolonging the overall positive sensations of joy and pleasure.

Leading Hypothesis – Synaptic Dopamine Levels Followed by the Consumption of Alcohol

Increased secretion of Dopamine to the synaptic cleft is associated with positive feelings and mood, while reduced levels below normal state concentrations are associated with “heavy” feelings and negative mood. Alcohol consumption causes an acute increase to Dopamine secretion which is then reduced by regulation mechanisms and overshoots sharply below normal state levels. By supporting the natural synthesis of Dopamine, high levels are maintained for prolonged time, enhance pleasuring sensations while negating undesired side effects.

C. Primary Validation of Hypothesis

To validate the hypothesis that increased neuronal Dopamine levels enhance the overall pleasuring experience during alcohol consumption, we have developed a nutritional formula consisting of L-Tyrone and Caffeine to promote Dopamine synthesis and help maintain long-lasting and readily available reserves – the “Euphoria” Formula.
The “Euphoria” formulation is based on scientific studies previously proving L-Tyrosine enhances neuronal Dopamine synthesis and release [1] and Caffeine upregulates the expression of the Tyrosine Hydroxylase enzyme in-vitro and in-vivo [2] [3].

The “Euphoria” Formula was experimentally tested and proven effective in a conducted study, as the combined intake of an alcoholic beverage (4.9% ABV beer) with the added formula significantly enhanced the uplifting sensations described by self-reporting participants for a prolonged period of time (compared to intake of same alcoholic beverage with no added formula).

The BAES (Biphasic Alcohol Effects Scale) Questionnaire – a self-report rating scale (0 to 10) designed to measure both the Stimulant and Sedative effects of alcohol – was used to conduct this study.

“Euphoria” Formula – Experimental Study Results

The results show that the consumption of regular alcoholic beer causes an initial rise to stimulant and uplifting effects followed by a sharp decline to below starting value. This decline is also correlated with gradual rise to sedative and depressing effects over time.
In comparison, consumption of beer enriched with the “Euphoria” Formula generated a significant increase to uplifting effects which was kept well above starting value for over two hours after consumption, while starting sedative values remained constant and showed no incline over time.
Initial examination of the Stimulant Effects results show that they correlate well with our hypothesis regarding neuronal Dopamine levels. Today, a follow-up study was conducted to examine direct relation between the two.

[1] Acworth, I. N. et al. (1988). ” Tyrosine: effects on catecholamine release.” Brain Res. Bull., 21(3), 473-7.
[2] McKenzie, S., Marley, P. D. (2002). ” Caffeine stimulates Ca(2+) entry through store-operated channels to activate tyrosine hydroxylase in bovine chromaffin cells.” Eur. J. Neurosci., 15(9), 1485-92.
[3]Datta, U. et al. (1996). ” Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment.” Neurosci. Lett., 220(2), 77-80.

D. Experimental Study and Results – Combined Intake of Alcoholic Beer with the "Euphoria" Formula

Following the “Euphoria” Formula development and positive preliminary testing, an experimental study was designed and conducted to attain quantitative data to support the formula’s potential to enhance the uplifting effects of alcohol consumption.

i. Protocol

Participants Population: The study was conducted on 198 healthy, non-alcoholic social drinkers (low to moderate weekly consumption of alcohol).
50% Women 50% Men
Ages 18-60 years (majority of 70% for ages 18-31)
Participants were told they are participating in a market research for a new beer product, with no additional information regarding the purpose of the study.

Study Design:

  1. Each participant took part in two separate study sessions: one control session and one study session.
  2. Both sessions had at least one week apart between them.
  3. The study was double-blind, with half of the participants doing the control session first and half doing the study session first.
  4. The primary tool that was used in this study to obtain quantitative results was the BAES self-reporting Questionnaire [WEB-LINK3. D. ii. The BAES Questionnaire], which was answered by participants before and after the consumption of alcoholic beer.
  5. During each session, participants initially answered the BAES Questionnaire to set their baseline values.
  6. Participants were then given 500ml of either a regular alcoholic beverage (4.9% ABV beer) for the control session or the same alcoholic beverage enriched with the “Euphoria” Formula for the study session.
  7. Participants were required to gradually consume the entire volume of their beverage in 15 minutes (approx. 100ml every three minutes) and then answered three additional BAES Questionnaires, each on a different time interval: 30, 60 and 120 minutes after consumption.

ii. The BAES Questionnaire

To properly study and establish the expected effects of the “Euphoria” Formula, a unique tool able to measure and quantify the alcohol-induced “euphoric sensation” was required. After examining several academically approved methods, we concluded that the most suitable tool for this objective was the Biphasic Alcohol Effects Scale (BAES) Self-Reporting Questionnaire [1].
The BAES Questionnaire is a reliable and validated systematic 14-item self-report scale designed to measure the Stimulant and Sedative effects of alcohol as separate and distinct constructs.
In the questionnaire, 14 items are presented in alphabetical order, 7 of which describe sensations associated with stimulant and uplifting effects, and 7 describe sensations associated with sedative and depressing effects. A participant answering the questionnaire is required to assign each of the 14 items with a number ranging from 0 to 10 to indicate how closely does each item expresses, corresponds or describes their current state, where “0” indicates “not at all” and “10” indicates “very much”.
The numerical indications of the stimulant and sedative effects are averaged to obtain two numerical values designated STIM and SED, respectively.

Items Associated with Stimulant Effects: Elated, Energized, Excited, Stimulated, Talkative, Up, Vigorous.
Items Associated with Sedative Effects: Difficulty Concentrating, Down, Heavy Head, Inactive, Sedated, Slow Thoughts, Sluggish

[1]Martin, C. S. et al. (1993). “Development and validation of the Biphasic Alcohol Effects Scale.” Alcohol Clin. Exp. Res., 17(1), 140-6.

iii. Results

BAES Questionnaires Results – Average STIM and SED Values with Standard Deviations

These results show that an alcoholic beer enriched with the “Euphoria” Formula significantly strengthens and prolongs the stimulant and mood elevating effects associated with alcohol consumption, as compared to a corresponding regular non-enriched beer, while significantly reducing and nearly nulling the sedative effects.
While the observed strengthening of the stimulant values over time correlates with our hypothesis regarding the formula’s ability to promote neuronal Dopamine synthesis [WEB-LINK – 3. B. Leading Hypothesis], the reduction of the sedative values is assumed to be a result of the change in activity ratio between the stimulant Dopamine system and other sedative systems that are regularly activated during alcohol consumption, such as the GABA system.

In a previously conducted BAES study [1], a similar rise to the STEM value was observed after 30 minutes when participants were administered 0.8 grams ethanol per kg bodyweight – equivalent to almost three times more alcohol than was consumed in our study.
While it is difficult to compare the two studies due to the subjective nature of the BAES Questionnaire, these give substantiate preliminary evidence to the effectiveness of the “Euphoria” Formula to enhance and prolong alcohol’s pleasuring and uplifting effects.

[1]Rueger, S. Y., King A. C. (2013). “Validation of the brief Biphasic Alcohol Effects Scale (B-BAES).” Alcohol Clin. Exp. Res., 37(3), 470-6.