The Neuroscience of Partying.

The Neuroscience of Partying

– A guide to mitigating the wear and tear from festival and party activities –

Video of lecture below

Text version of lecture.

With recreational drug use on the rise, and an increasing popularity of EDM, music festivals and nightlife events, it’s important for us to educate people to keep them safe. With many recreationally substances being name illegal to consume, it can be difficult for people to get an accurate depiction of which drugs actually have the most risks. This article is a textual source of Caitlin Thompson’s workshop/lecture material presented at music festivals and other party events. Caitlin’s presentation, titled “The neuroscience of Partying” is a guide for party-goers that offers information on drug effects, interactions and harm-reduction methods to mitigating the wear and tear of festival activities. Topics covered include how specific drugs affect neurotransmitters systems in the brain, which drug interactions to avoid, and how to nutritionally combat the depletion and damage from partying.

What Are We Actually Doing At Festivals/Raves/Parties?

To start off, lets examine what we’re actually doing at a music festival or similar event. Well, most of us aren’t sleeping very much. Sleep deprivation is a huge part of party lifestyle across the board, no matter if it’s a rave, concert, night at the bar, or weekend in vegas. We also tend to be in highly stimulating environments that excite our nervous systems. Overexertion is another key player in the typical festival experience. Sometimes venues can be large and spread out, requiring us to walk, or bike great distances over the weekend. And that’s in addition to our enthusiastic dancing, laughing and socializing. People also tend to not drink enough water during these events, leading to dehydration. Water is vital to many cellular processes and having low supply may inhibit you’re body’s optimal functioning. In some cases however, people can drink TOO MUCH water and cause their cells to fill like balloons, and pop. This happens when the body does not have enough electrolytes such as salt to balance the fluid in the body inside and outside of cells. It’s important to have minerals/electrolytes to avoid this problems. Coconut water and healthy snacks are good ways to restore this balance. Then last but not least, people are consuming alcohol and drugs. SHOCKING, I know. This is a huge part of party culture, and will not change anytime soon.

So we have this stuff going on.

Sleep deprivation
Over-stimulation
Overexertion
Dehydration
Use of alcohol, caffeine and other drugs.

What does all that mean on a physiological level though? What are these things actually doing to my body?

Sleep deprivation is probably what causes the most damage out of any of these things. Sleep is a very important time when the most of the body’s restorative and repair processes are happening. We use the time we sleep to build new molecules, remove toxins and repair damaged tissue. When we deprive our body’s of sleep, things like oxidative stress and inflammation take a toll on our cells and start to damage them. Over-stimulation, although fun, activates brain cells frequently, exhausting them and causing them to burn out from something called “excitotoxicity”. This process is also related to oxidative stress and damage. When talking about something being neurotoxic, we are really referring to it’s ability to damage cells through oxidation. Oxidation is caused by free-radicals in the body that steal electrons from other molecules in an effort to satisfy it’s own electron count to an even number. Electrons liked to be paired, and when a odd-electron-numbered free radical comes along, it steals electrons from other atoms belonging to cells, damaging structures and creating a domino effects of electron stealing. More or less, all cellular and tissue damage comes down to oxidative stress, which is a normal part of human life. Oxidation is happening all around us everyday. It’s what’s makes nails rust and crackers get stale. Oxidation is the process by which we age. Luckily, our body makes and consumes antioxidant molecules to neutralize these harmful free-radicals that cause oxidation. This is why we don’t rust like a chain link fence. Our body is constantly scavenging these molecules to keep our cells neutral. By skipping out on sleep, we are using up our body’s antioxidant resources and depleting our supply until our next sleep.

When we have oxidative damage going on in our body, our immune system launches an attack, presuming there is a pathogen responsible for the damage. It sends pro-inflammatory cytokine molecules to clean up the mess. Unfortunately a lot of times the immune system can be a bit overambitious and accidentally damage healthy tissue in the process. This leads to inflammation, and further damages tissue and cells. This is the same reason we ice an injury to reduce inflammation.

During sleep, much of our neurotransmitter levels are restored. Without it, we use up our supply, and drugs that increase neurotransmitter release deplete it even faster. Our body may be using all it’s energetic, vitamin and mineral resources to repair a body that is being overexerted, and may not have an abundant supply left to allocate to neurotransmitter production.

So party activities contribute to

Oxidative stress
Inflammation
Depletion of neurotransmitters, vitamins, minerals and antioxidants.
Cellular/tissue damage.

Here is a picture of healthy brain matter (neurons) and inflamed/damaged brain matter. You can see that the picture on the left has many more axons and dendrites and is healthier than the picture on the right, which shows reduced dendrites and axons, due to degeneration, or atrophy from inflammation.

What does this translate to as far as behavior and mood goes?

Exhaustion
Feelings of Depression
Brain Fog
Trouble focusing
Irritability

None of after-effects are fun. Lets learn a bit about neuroscience and tactics on how we can prevent the wear and tear of festival life to stay healthy and happy.

Neuroscience Mini Lesson

Here’s a quick mini lesson in neuroscience. I’m going to go over a handful of neurotransmitters, even though there are hundreds. These are the important ones and the ones most relevant to recreational activities.

Glutamate: Glutamate is the most abundant neurotransmitter in the entire body. It is an excitatory neurotransmitter and it’s activity is mandatory for exciting a neuron or brain cell and causing an action potential. An action potential is an electrical signal created by the activation via glutamate. It travels down a nerve cells long axon structure where it reaches the end, and releases neurotransmitters into the synapses to signal neurotransmitter release which may activate the next cell continuing the electrochemical signal.

GABA : GABA is an inhibitory neurotransmitter. It’s role is to dictate whether glutamate activity produces an action potential or not. It can prevent an action potential by inhibiting and overriding glutamate’s activation. GABA is very important for regulating neuronal activity and keep cells from being overstimulated and short-circuiting. Glutamate and GABA have a push pull relationship that is optimal when balanced, preventing over excitation, or lack of excitation. Many drugs with a sedating affect either involved GABA, or block glutamate activity, producing similar downing effects.

Serotonin: Serotonin is a very important neurotransmitter for regulating sleep, appetite and mood. It promotes feelings of calmness, peace and well being. Interestingly, 80% of our serotonin receptors are in our gut, emphasizing it’s importance in eating behavior.

Dopamine: Dopamine is largely involved in motor control, cognition, behavior, states of arousal and reward circuitry. Dopamine is whats responsible reinforcing behaviors by producing a feel-good euphoria. This applies to addiction behavior as well, which many addictions causing a release in dopamine.

Pictured above is a neuron, or brain cell. Long branch-like structures called dendrites connect with dendrites on other cells. Tiny little protrusions on the ends are called synaptic spines and contain a very small gap between them called the synpases. One cell releases a cocktail of neurotransmitters such as glutamate, or dopamine into the synapses. The neurotransmitters bind to receptors on the receiving cell, and carries on the signal. This is how electrochemical signaling works. Messages can be passed down long networks of cells via this domino chain effects of cell to cell communication.

What happens when oxidation gets involved though? When a nerve cell is excited, perhaps by glutamate, free radical molecules are naturally released. This leads to oxidation, which our body neutralizes with antioxidants. When stimulation is excessive, and or antioxidant levels are low, this can lead to oxidative damage to brain cells. This results in shriveling or damage to dendrites and synapses, and even totally cell death. Death of dendrite structures and whole brain cells results in brain atrophy and reduced cognitive ability. It also is associated with depression, alzheimers, parkinson’s and other neurodegenerative diseases. When synaptic connections are damaged, cell to cell electrochemical signaling is inhibited because there is a lack of available connection sites. This can results in lower levels of serotonin and dopamine signaling, even when there are abundant supplies of serotonin and dopamine. This is one theory for the mechanism of depression. Recent research is suggesting it is mostly due to the damage from oxidative stress and inflammation that causes depression, rather than low supplies of neurotransmitters like serotonin, though both may be a factor.

Recreational Drugs

Here I’ve made a very generalized categorization of popular recreational drugs and put them under the group that they most dominantly effect. Many drugs interact with multiple neurotransmitter systems, but for simplicity, I labeled them under system they affect the most. Alcohol is probably the most promiscuous of any of the drugs listed, seeing as how it interacts with almost every major neurotransmitter system.

Serotonergic drugs:

MDMA, Psychedelics (LSD, psilocybin, DMT, mescaline etc.), synthetic analogues (2C-B, 2C-I, DOB, N-BOMB, 2Ct27 etc).

Dopaminergic:

Cocaine, methamphetamines and amphetamines, opioids (heroin, percacet, methadone), nicotine.

GABAergic:

Alcohol, GHB, valium, Xanax

Glutaminergic (blocking):

Ketamine, Nitrous oxide, PCP.

Endocannabinoid:

Marijuana, synthetic cannabinoids (spice)

While MDMA is technically in the amphetamine drug class, it’s labeled under serotonergic because it is unique in it’s nature to affect the serotonergic system more dominantly than other amphetamines which are typically primarily dopaminergic. The psychedelic drugs are usually serotonin agonists, meaning that their molecules fit into serotonin receptors, stimulating the receptor in a similar way to serotonin molecules. Serotonin agonists differ from drugs like MDMA because MDMA uses 80% of your body’s own supply of serotonin to dump into the synapses. This is different than activating a serotonin receptor with something that is not serotonin. They can create similar effects, but MDMA depletes your body’s supply, and you have to replenish those serotonin levels afterwards, while psychedelics do not use up your body’s neurotransmitters resources. The synthetic serotonergic analogs should be taken with caution. Many of them have neurotoxic properties, are poorly studied, and have been reported to even cause fatalities. The classical psychedelics do not display toxicity and there is no known fatal dose.

The dopaminergic drugs are typically the one’s most strongly associated with addiction. Dopamine plays a crucial role in the brains reward systems and release of dopamine reinforces behaviors. Dopamine’s activity is also typically what makes something neurotoxic or not. Although dopamine is a neurotransmitter, it is also a neurotoxin. The natural metabolism of dopamine to free-radical metabolites causes oxidative damage to cells. The more dopamine activity stimulated by a drug, the more neurotoxic potential it has. Even though MDMA is listed primarily as a serotonergic drug, it also induces release of dopamine. This dopamine release is what gives MDMA it’s neurotoxic properties.

Drugs that affect GABA systems are typically GABA agonists, meaning they fit into the GABA receptor similarly to GABA itself. Activating GABA receptors displays inhibitory effects on neurons and often causes a calming, or sedative affect.

A majority of recreational drugs affecting glutaminergic systems are antagonists, meaning they block glutamate activity by binding to receptors but not activating them. This blocks the activation of the receptor by excitatory glutamate molecules. These drugs can actually reduce excitotoxic damage by reducing the amount of excitation of the nervous system. Nitrous oxide is a non-toxic drug of this group.

Drug interactions

Here’s a chart for a more detailed picture.

Alcohol: As mentioned before, alcohol affects many different neurotransmitter systems. For this reason, it is particularly dangerous to mix with other drugs. Alcohol should be avoided with cocaine, amphetamines, MDMA, opioids, ketamine, many pharmacueticals and GHB.

MDMA: Caution should also be taken with mixing MDMA and other drugs. MDMA inhibits CYP 450 enzymes in the liver that are responsible for drug metabolism. This can interfere with your body’s ability to normally breakdown drugs and could contribute to toxic or prolonged effects.

Opioids, Methamphetamines, Cocaine: All of this drugs have high risk when mixed with others drugs, especially when mixing with eachother. Because of the strong dopamine activity of these drugs, they should never be combined with eachother, alcohol, MDMA or prescription drugs.

SSRI’s:

SSRI’s (selective serotonin reuptake inhibitors) are widely prescribed as antidepressants. They block the reabsorptions of serotonin into the releasing neuron, trapping it into the synapse making it more available for binding to a receptor. MDMA and other drugs have similar effects. This makes them very dangerous to mix with SSRI antidepressant. The combined effects of multiple drugs blocking the serotonin reuptake can cause an overload of serotonin in the synapse, having toxic effects. This can result in serotonin syndrome, which can cause brain damage and even death.

MAOI’s

MAOIs (Mono Amine Oxidase Inhibitors) are another class of drugs typically used to treat depression. In our body’s, we have an enzyme called mono amine oxidase that is responsible for degrading neurotransmitters such as serotonin and dopamine, to regulate the body’s circulating supply. By inhibiting this enzyme with a drug, you get elevated levels of serotonin, dopamine, norepinephrine and other neurotransmitters. This, like SSRI’s can cause an excess of certain neurotransmitters in the synapse and lead to toxicity and damage.

It is best to avoid taking medications with drugs.

What can you do to be safe?

Drug reagent tests- Dancesafe.org offers drugs testing kits that can give you chemical information about your drugs. They can tell you if MDMA, amphetamines, piperazines and other drugs are present.

Pillreports.com– Pillreports is a great tool. It is a online database full of different pills circulating the black market. People test them with kits, or by taking them, and write detailed reports with pictures, helping you identify your pill’s batch and deciding if it is the quality you feel safe consuming.

“If it’s bitter, it’s a spitter” – LSD has no color- odor or taste. If you take a liquid drop, or blotter tab that has a bitter flavor, you may want to quickly spit it out. Chances as it is not truly LSD and could be a toxic, understudies research chemical or LSD analogue.

Don’t mix drugs!– Mixing drugs complicates things and can be deadly. If you’re going to mix them, please refer to the chart above and make responsible decisions about which drug combinations your toy with.

How can I replenish my body’s resources and neurotransmitters to combat the wear and tear of partying?

There are ways to use nutrition to replenish key nutrients that will help your body rebuild neurotransmitters and repair the oxidative damage that’s results from partying. Obviously eating healthy, organic and whole foods is a great idea. Protein and raw fruits and vegetables are a great start. Coconut water is another great tool. But lets go deeper than the obvious.

Amino Acids

Amino acids are the building blocks of protein. When we eat protein, we get amino acids. Many neurotransmitters are created from amino acids. Serotonin is made from L-tryptophan. In the body, L-tryptophan is converted to 5-HTP( 5-hydroxy tryptophan) and then to 5-HT (5-hydroxy tryptamine) which is a fancy way of saying serotonin.

Dopamine is created from the amino acid, L-tyrosine (and also L-phenyalanine). These amino acids can be eaten as protein from food, or taken as supplements. Unfortunately, most plant sources of protein are scarce in these 2 specific amino acids. They are most abundant in animal proteins such as meat, dairy, and eggs.

B Vitamins-

B vitamins are essential for brain health and repair. Many of them play a crucial role in creating neurotransmitters by assisting in the enzymatic conversion of the amino acids to their respective neurotransmitter. When someone is deficient in B vitamins, the body’s natural cellular processes get disrupted and will lead to glutamate excitotoxicity and imbalance in oxidation and reduction reactions in the body. They are also important for repairing, replicating and methylating DNA.

Magnesium-

Magnesium is an important mineral that is responsible for over 300 different enzyme reactions in the body. It also contributes to brains cells ability to repair themselves and blocks excessive glutamate activity, protecting from excitotoxicity.

Antioxidants-

As explained before, much of the physical damage is caused by oxidative stress. This can be combatted with antioxidants. Plants or supplements with many polyphenolic antioxidant compounds are a great way to recover. Turmeric, blueberry, milkthistle, spirulina and ashwagandha are some potent antioxidant containing plants. By neutralizing oxidation with antioxidants, you reduce and prevent inflammation and damage to your neurons.

Promote brain cell growth and repair?

There are a number of things that actually promote growth and repair of brain cells and their synpases. Turmeric and blueberry exhibit this property, as well as exercise, listening to music, meditation, and fasting. The classical psychedelic drugs also promote new cell growth and contribute to neuroplasticity in the brain.

Many of the ingredients mentioned in this article are available as supplements. If you’d like to save yourself the trouble of getting all these items separately, EntheoZen offers product called Weekend Warrior that was designed specifically for party-recovery. It contains many of the ingredients discussed and has been consciously crafted to combat the depletion or nutrients and oxidative stress from partying.

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