Drugs, Neuroscience, and You


Let’s be honest here: if a person really wants to try an illegal drug, he or she is going to find a way to try it. To me, the most reasonable response to this fact seems to be to share clear, science-backed explanations of the effects and risks involved with each drug.

So today, I’m going to take a little break from my usual newsy reporting, and provide a condensed rundown on some drugs, in the style of my Memory Menagerie write-up.

First, just a couple quick notes about this summary. For one thing, it’s going to focus on drugs that are illegal in many places, for the simple reason that it’s (understandably) not easy to get clear scientific info about them. (If you’re interested in a similar write-up about psychiatric prescription drugs, though, drop me a comment and I’ll happily write one.) Anyway, my goal here is to inform and educate – not to advise or condone anything. To be annoyingly literal about this: I’m not suggesting that you take illegal drugs.

Second, I also can’t cover every drug that’s available today – spend a few minutes on Erowid.com, and you’ll see that there are dozens, if not hundreds of them. So I’m going to stick to the ones you’re most likely to hear about. And that brings up my final note: my main goal here isn’t to be exhaustive or in-depth, but to provide a quick overview of major “street drugs” on a single page, simply because one-page collections of quick scientific info on illegal substances are (oddly enough) hard to come by.

And now, without further ado…let’s talk about some drugs.

Cannabis (marijuana)1

What it is: A resin that grows on the female buds of plants in the genus Cannabis. The word “marijuana” seems to have first come into use as a slang term (of unknown origin) in Mexico in the 1800s.
What it does: Physically, ingestion of the drug causes bloodshot eyes, dry mouth, increased heart rate, and muscle relaxation. Mentally, it produces a “high” – a feeling of euphoria. Beyond this, its psychological effects vary widely from user to user. Some common effects, though, include reduction of stress-related feelings, increased appreciation of art and music, increased tendency to laugh, increased appetite, a distorted sense of time, a variety of degrees of amnesia, and a tendency toward metacognition (thinking about thinking) and introspection. Another notable aspect of the high is that certain internal thoughts – especially those linked with strong emotion – seem extraordinarily vivid. If someone with an anxiety-related disorder uses cannabis, these effects can become tinged with negativity, and paranoia may set in, sometimes leading to a panic attack. As with many drugs, the boundary between positive and negative effects is easily crossed, and constant careful monitoring of one’s set and setting is crucial. Depending on the dose, effects can last from 30 minutes to eight hours. Though this drug is not chemically addictive, a large number of users develop a psychological dependency on it.
How it does this: A variety of cannabinoids bind to a range of receptors involved in the body’s natural endocannabinoid system, which blocks communication between neurons within their own areas.  Most prominent among the cannabinoids in cannabis is Δ9-tetrahydrocannabinol, often known as THC. It binds to CB1 and CB2 endocannabinoid receptors in a wide range of brain areas, including the amygdala, the hippocampus, and the nucleus accumbens. The exact relationship between the neurochemistry of the “high” and many of the side effects above remains poorly understood.

Cocaine (coke)

What it is: A crystalline alkaloid, a chemical compound found in the leaves of the Coca plant. It was first isolated by the chemist Friedrich Gaedcke in 1855.
What it does: Physically, cocaine acts as a stimulant, raising heart rate, increasing feelings of energy, raising confidence and enthusiasm, and providing an otherwise euphoric and alert “high.” Cocaine also acts as a mild to moderate local anesthetic. In many users, the drug also greatly reduces patience and attention span, and contributes to feelings of anxiety or paranoia, especially after repeated use. Effects usually last from 15 minutes to an hour. This drug is highly addictive – withdrawal symptoms can include irritability, anxiety, fatigue, anhedonia (inability to feel pleasure) and insomnia.
How it does this: Cocaine molecules bind to sites on neurons called dopamine transporters, which normally help reabsorb dopamine – a neurotransmitter involved in feelings of reward – for future use. When the cocaine molecules bind to the dopamine transporters, they block these transporters’ function, keeping dopamine in the synaptic clefts much longer than usual. The result is that many brain pathways – in regions like the nucelus accumbens, the ventral tegmental area, and the prefrontal cortex – are bathed in dopamine, raising reward feelings far above the norm.

Psilocybin (mushrooms)

What it is: A chemical produced by more than 200 species of mushrooms – but mainly associated with the mushroom Psilocybe mexicana.
What it does: Physically, the drug tends to cause lethargy and drowsiness, disorientation, intensified reflexes, pupil dilation, and increased heart rate. As with most psychedelics, psychological effects vary widely from person to person, and depend heavily on set and setting. Feelings of euphoria or depression are common, as are enhanced appreciation of colors or shapes, and a distorted sense of time. Closed- and open-eye hallucinations vary from mild to intense depending on the dose, and can range from simple moving colors, shapes and patterns all the way to entheogenic experiences and dialogues with hallucinated beings. Effects can last from six to twelve hours, or possibly longer.
How it does this: The human body rapidly converts psilocybin to psilocin, a chemical that acts as a partial agonist to several types of serotonin receptors, especially the 5-HT2A receptor (serotonin is also known as 5-hydroxytryptamine, or 5-HT). Serotonin’s exact role in psychedelic effects remains poorly understood, but it’s known that this neurotransmitter is involved in regulating moods, and increasing feelings of well-being.

LSD (acid)

What it is: A semi-synthetic chemical originally derived from ergotamine, a substance found in ergot, a fungus that often grows on rye grain. It was first synthesized by the chemist Albert Hofmann in 1938, but he didn’t make his first (self-administered) test of LSD until 1943.
What it does:
Physically, the drug raises alertness, causes pupil dilation, raises or lowers body temperature, and increases or decreases appetite. As with most psychedelics, LSD’s psychological effects vary widely from person to person, and depend heavily on set and setting. Many users perceive movement of static surfaces like walls, as well as intensified perception of colors, brightness, iridescence, and shininess. Higher doses can trigger closed- or open-eye hallucinations of geometric patterns, echo-like distortion of sounds, and synaesthesia. Because the drug often intensifies emotions, some users can descend into “bad trips” involving panic attacks or even fragmentation of identity. However, the overall euphoric “high” sustained by LSD means a calming friend can sometimes help turn a bad trip back into a positive one. Effects usually last from four to twelve hours.
How it does this: LSD binds to many types of serotonin receptors, including 5-HT1A, 5-HT2A, 5-HT2C, 5-HT5A, and 5-HT6. At 5-HT2A, in particular, it acts as a strong partial agonist, helping trigger the release of glutamate throughout the cerebral cortex. Some research suggests that LSD may preferentially bind to less-used 5-HT receptors, triggering synaptic activity along little-used pathways. Exactly how all this contributes to the drug’s psychedelic effects remains poorly understood, but it’s likely to be linked with serotonin’s excitatory effects in the prefrontal cortex.

Salvinorin A (salvia)

What it is: A chemical found in the plant Salvia divinorum, a member of the sage family.
What it does: As with most psychedelics, salvinorin’s psychological effects vary widely from person to person, and depend heavily on set and setting. Some common effects include uncontrollable laughter, sensations of movement, distortions of time, distortions of body boundaries and perceived location, closed- or open-eye hallucinations of membranes or geometric patterns, vivid reliving of memories, synaesthesia, and glossolalia. Some users report feelings of euphoria, while others descend into fits of rage or panic attacks. Length of effects varies widely depending on the dose and method of ingestion – the experience can last from one minute to several hours.
How it does this: Salvinorin is a strong agonist for the κ-opioid receptor, and an even stronger partial agonist for the D2 dopamine receptor – thus, it increases availability of opioids and dopamine. Research on where this activity is mainly targeted, and what its relationship is to salvinorin’s psychedelic effects, remains in very early stages. Interestingly, though, salvinorin has no affinity for the 5-HT2A serotonin receptor, which is heavily affected by drugs like psilocybin, LSD, and mescaline – so salvinorin’s effects may be produced via entirely different neurochemical pathways.

MDMA (ecstasy)

What it is: A chemical first synthesized in 1912 by Merck chemist Anton Köllisch; its original intended use was to stop abnormal bleeding. It was derived from safrole, an oil extracted from the sassafras plant.
Important note: The term “MDMA” refers to the pure chemical; many tablets described as “ecstasy” also contain other substances, such as dextromethorphan or amphetamine.
What it does: Both physically and psychologically, the effects of the drug are more similar from user to user than those of many psychedelic drugs. Physically, it causes loss of appetite and exerts tension on muscles, which often results in behaviors like mild twitching or jaw-grinding. Psychologically, its most notable effect is that it raises alertness and produces a euphoric mental state, characterized by high energy, strong feelings of empathy and intimacy, heightened self-confidence, and sexual arousal. Effects last from 1.5 to 3 hours. The “comedown,” (i.e., aftereffects) of ecstasy can include dysphoria (feelings of unpleasantness), anxiety, and – in some cases – even prolonged depression.
Why it does this: MDMA triggers neurons to release serotonin, dopamine and norepinephrine. By blocking the actions of the vesticular monoamine transporter protein, which normally would help reabsorb norepinephrine, MDMA prolongs and heightens the availability of this neurotransmitter. It also acts as a weak agonist at 5-HT1 and 5-HT2 serotonin receptors, which increases the concentration and availability of serotonin – LSD acts as a partial agonist at some of these same receptors. Some scientists have suggested that MDMA also increases availability of oxytocin, the hormone present in high concentrations in a mother’s body during childbirth.

Nitrous oxide (balloons)

What it is: A chemical compound composed of sets of two nitrogen atoms bonded to one oxygen atom, usually in gas form.
What it does: At low doses, nitrous oxide has an anti-anxiety effect. It also produces dizziness, euphoria, and a feeling of being intensely in tune with somatosensory sensations. Effects often last only a few minutes, though they can be prolonged by repeated doses over a given time period.
How it does this: Nitrous oxide activates dopaminergic neurons in the ventral tegmental area and nucleus accumbens – areas known to be involved in addiction and reward. It also moderately blocks NMDA glutamate receptors, which play crucial roles in memory and learning, as well as β2-subunit-containing nicotinic acetylcholine (ACh) channels,which respond to nicotine-like chemicals. Meanwhile, it weakly inhibits AMPA and kainate glutamate receptors, GABAC receptors, and 5-HT3 serotonin receptors, while potentiating GABAA and glycine receptors – all of which modify synaptic likelihood and range in a wide variety of ways.

GHB (G)

What it is: An acid that naturally occurs in small amounts in the central nervous systems of most animals. Synthesis of the chemical was first reported in 1874 by chemist Alexander Zaytsev.
What it does: Though it’s sometimes described as “liquid ecstasy” (i.e., MDMA), GHB can produce a much broader range  of effects than MDMA does, depending on the dosage. At low to moderate doses, its effects are indeed very similar to MDMA: it acts as a stimulant and produces euphoria, decreased anxiety, and increased sociability – often with a more serene emotional tenor than the typical MDMA experience. At higher doses, though, it can act as a dissociative or a sedative, and has even been reported to trigger “blackout” fugue states in some users. Depending on the dose, effects may last from 1 to 5 hours.
How it does this: GHB is an agonist at the excitatory GHB receptor, and it’s a weak agonist at the GABAB receptor, which is inhibitory. GHB induces the accumulation of either a derivative of tryptophan or tryptophan itself in the extracellular space, possibly by increasing tryptophan transport across the blood-brain barrier. Activation of the GHB receptor in some brain areas seems to contribute to the release of the excitatory neurotransmitter glutamate. Interestingly, low concentrations stimulate dopamine release via the GHB receptor, while higher concentrations inhibit dopamine release via GABA(B) receptors.

2C-B (nexus)

What it is: A chemical first synthesized as an anesthetic by chemist Alexander Shulgin in 1974.
What it does: At low doses, many users experience aphrodisiac effects, increased energy, and euphoria. Moderate to high doses can result in jittery feelings, a tendency toward “giggliness,” increased attention to one’s body and thought processes, and difficulty holding one’s concentration on a task (executive attention). Higher doses can produce unique visual and auditory hallucinations – objects can take on “runny” shapes or “watercolor-like” colors. At high doses, these may become full-blown hallucinations; i.e., independent of the user’s actual visuals. Depending on the dose, these effects can last from 1 to 5 hours – but the drug is known to leave residual effects with some users (i.e., the effects of the drug may still be experienced for several hours after the user’s body has metabolized the entire dose); this seems to be more common with higher doses. The “comedown” period has been associated with irritability, headaches, etc., but not all users report these symptoms.
Why it does this: Unlike most hallucinogens, 2C-B has been shown to be a low efficacy serotonin 5-HT2A receptor partial agonist or even full antagonist. This means its effects are produced by other neurochemical pathways than the serotonin pathway used by drugs like LSD and mescaline. Though it’s known that 2C-B contributes to the formation of several chemicals in the liver, their role in its effects is still poorly understood.

Ketamine (special K)

What it is: A chemical first synthesized as an anesthetic by pharmaceutical company Parke-Davis in 1962.
What it does: The drug produces a feeling of “dissociative anesthesia” – a sense of depersonalization or detachment from one’s body. As with other dissociatives, this state is often accompanied by a feeling of euphoria – the tendency of users in dissociative states to report decreased fear responses may also contribute to this feeling. At higher doses, ketamine can result in hallucinations (typically simple closed- or open-eye visuals), and sometimes in the strong dissociation commonly known as a “K-hole,” which is thought to mimic the psychological effects of schizophrenia. Effects often last 60 minutes or shorter.
How it does this: Ketamine acts as an NMDA receptor antagonist. At high, fully anesthetic level doses, ketamine has also been found to bind to type 2 opioid μ receptors, both of which contribute (along with its general tendency to block sodium channels) to its anaesthetic and analgesic effects. It acts as a dopamine reuptake inhibitor, increasing the availability of that neurotransmitter. Effects seem to be primarily focused in the hippocampus and the prefrontal cortex.

PCP (angel dust)

What it is: A chemical first synthesized as a surgical anesthetic in 1926.
What it does: Physically, low doses produce numbness, loss of balance, and slurred speech, while higher doses have analgesic and even anesthetic effects. Psychologically, users report euphoria, increased self-confidence, feelings of invulnerability, changes in body image, and loss of ego boundaries. Higher doses have been reported to lead to paranoia, hallucinations, depersonalization, and suicidal impulses. Depending on the dose, effects may last from 1 to 6 hours.
How it does this: PCP’s primary action is as an antagonist at on glutamate receptors, such as the NMDA receptor – this inhibits the release of the excitatory neurotransmitter glutamate, which is likely a cause of effects like loss of ego boundaries and depersonalization. PCP also inhibits nicotinic acetylcholine receptors – and, like ketamine, it acts as a partial agonist at D2 dopamine receptor sites, contributing to feelings of reward and euphoria.

Mescaline (peyote)

What it is: An alkaloid that occurs naturally in several types of cactus, most notably the peyote cactus (Lophophora williamsii).
Important note: the terms “mescaline” and “peyote” aren’t strictly synonymous; the peyote cactus contains a large spectrum of psychoactive  phenethylamine alkaloids, of which the principal one is mescaline.
What it does: The visual distortions produced by mescaline are somewhat different from those of LSD – rather than perceptions of non-existent objects or persons, they tend to enhance subjective perceptions and modify them in ways that many users find difficult to describe in words. Color and shape are greatly enhanced, and users report experiencing an overwhelming sense of the unique “is-ness” of individual objects. As with LSD, synesthesia is also common. Effects typically last for 12-18 hours.
How it does this: Neurochemically, mescaline acts similarly to other psychedelic drugs like LSD and DMT – it binds to and activates the serotonin 5-HT2A receptor with a high affinity as a partial agonist. How this leads to psychedelic effects is still poorly understood, but it likely involves excitation of neurons in the prefrontal cortex. Mescaline also activates the 5-HT2C serotonin receptor. In addition to serotonin receptor activity, the drug also stimulates dopamine receptors.

5-MeO-DMT (DMT)

What it is: A chemical compound that naturally occurs in small quantities in the central nervous systems of many animals, and is often made from the bark resin of Virola trees. It was first synthesized in 1936 by chemist Richard Manske.
Important note: Although 5-Me-O DMT is often referred to as “DMT,” the two terms are actually not synonymous: 5-Me-O DMT is a close relative  of the chemical DMT, but it’s approximately 4 times as potent. Still, the pharmacology and range of potential effects for both chemicals are highly similar.
What it does: At low doses, DMT and its relatives produce somewhat similar effects to those of psychedelics like LSD and 2C-B – increased appreciation for light, color, and sound, and enhanced brightness and “watercolor-like” colors. At higher doses, the drug can produce powerful entheogenic experiences including intense visuals, euphoria and hallucinations. Effects often last only 5 to 10 minutes, but users have reported that a full-blown “trip” can be shocking in its alienness and intensity.
How it does this: Like other hallucinogens such as LSD and mescaline, a large part of DMT’s psychedelic effects are linked to the drug’s activation of the 5-HT2A serotonin receptor – though, as with these other drugs, the exact linkage between 5-HT receptors and psychedelic effects is poorly understood. Psilocin, an active chemical in many psychedelic mushrooms, is structurally similar to DMT.

Ayahuasca

What it is: A chemical stew of various psychoactive substances prepared from the South American Banisteriopsis caapi jungle vine. Its usage in certain tribal rituals dates back hundreds – if not thousands – of years.
What it does: Ayahuasca is essentially a preparation specially crafted to allow DMT to be deliverable to the brain when taken orally – so most of its effects are highly similar to those listed in the “5-MeO-DMT” entry above. The chemicals harmine and harmaline – other ingredients in the brew – can cause severe nausea and vomiting, which some users say enhances the intensity of the psychedelic experience.
How it does this: Ordinarily, the chemical MAO-A prevents DMT from crossing the blood-brain barrier – but the chemicals harmine and harmaline are selective and reversible inhibitors of MAO-A, while tetrahydroharmine is a weak serotonin uptake inhibitor. This inhibition of MAO-A allows DMT to diffuse unmetabolized past the membranes in the stomach and small intestine and eventually get through the blood-brain barrier (which, by itself, requires no MAO-A inhibition) to activate receptor sites in the brain.

Methamphetamine (meth)

What it is: A chemical first synthesized from the herb ephedrine by chemist Nagai Nagayoshi in 1893. Fun fact: in World War II, the Japanese military stockpiled vast amounts of this drug, and handed it out to soldiers before battles.
What it does: Physically, the drug often increases heart rate, raises body temperature, and causes tremors or twitching. Psychologically, it creates euphoria and aids concentration – especially on menial and repetitive tasks – increases libido, and raises self-confidence and feelings of power. Higher and/or repeated doses can lead to dermatillomania (compulsive skin picking), hallucinations, paranoia, and sometimes even psychosis. Depending on the dose, effects can last from 3 to 12 hours. This drug is highly addictive, and many former users experience anhedonia (inability to feel pleasure).
How it does this: Methamphetamine causes the norepinephrine, dopamine, and serotonin (5HT) transporters to reverse their direction of flow, leading to a release of these neurotransmitters into the synaptic cleft. The drug also indirectly prevents the reuptake of these neurotransmitters, causing them to remain available for a prolonged period. This leads to feelings of euphoria and reward – and, over time, also contributes to paranoia and addiction.

Heroin

What it is: A chemical first synthesized from the opioid drug morphine by C. R. Alder Wright in 1874. The usage of opium dates back at least to the third millennium BCE, if not earlier.
What it does: Because heroin is essentially a concentrated form of morphine, which in turn is essentially a concentrated form of opium, this entry will deal with the similar effects of these three related drugs. Users of all three report an intense “rush,” and an acute, transcendent state of euphoria. Many users also report anesthetic and analgesic effects. Depending on the dose and the method of administration, effects may last from 30 minutes to 3 hours. This drug is highly addictive – withdrawal symptoms include dysphoria (feelings of displeasure), anxiety, nausea, diarrhea, fever, restlessness, and insomnia.
How it does this: When taken orally, heroin is metabolized in the digestive tract, delivering morphine to the body and brain. When injected, the drug quickly crosses the blood-brain barrier and is converted into morphine there. In either case, morphine binds to μ-opioid receptors, creating euphoria, analgesia, and anti-anxiety effects. It also stimulates histamine release, leading to a “body high” for many users.

…and there you have it. I’ll do my best to keep updating, refining, and adding to this over time; but for now, I just wanted to make sure it’s available.

___________

1. For all these drugs, I’m going to provide the “real” name, and the most common “unofficial” name. Every drug is known by loads of other slang terms, and more are being coined all the time. My goal isn’t to list them, but simply to make it clear what drug I’m talking about.

  1. February 22nd, 2012
  2. March 6th, 2012

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