The Major Drug Classes and Their Subjective Effects
There are thousands upon thousands of psychoactive compounds and seemingly millions of different possible effects! How do we make sense of all of this? Is there a catalog of all the possible types of drugs and what they do?
Well of course, dear reader! Today we are going to go over
The Major Drug Classes and Their Subjective Effects
Note that this article will primarily be focusing on the subjective experience of these drug classes. We will briefly mention the pharmacodynamic mechanisms of action for these drugs but mostly in the interest of categorization. We will dive more in depth about these different MoAs in future pharmacology articles and drug deep dives.
Let's Begin...
Stimulants
Stimulants are drugs that primarily have an activating or stimulating effect on the user. These are drugs that tend to bias the user towards action and wakefulness, and are frequently used pharmaceutically in the treatment of ADHD and other related disorders. Recreationally, these drugs tend to be known for their intense euphoria, and this is one of the most commonly abused classes of drugs out there.
A well known recreational stimulant... And some cocaine next to itSUBJECTIVE EFFECTS:
Euphoria, Pro-Social Behavior, Talkativeness, Stimulation, Motivation, Thought Acceleration, Reward Driven Behavior, Time Compression (Time speeds up), Loss of Appetite, Wakefulness, Insomnia, Anxiety, Paranoia, Psychosis, Focus Enhancement, Hyperfocus, Pro-Sexual Behavior, Horniness, Reduced Refractory Period in Men, Excess Movement, Delayed Orgasm, Intensified Sexual Pleasure, etc
EXAMPLE DRUGS:
Adderall (Mixed Amphetamine Salts), Clobenzorex, Vyvanse, Dextroamphetamine, Methamphetamine, Cocaine, 2-FMA, 2-FA, APVP, APHP, Modafinil, Caffeine, NEP, Theobromine, Ritalin (Methylphenidate), etc
MECHANISM OF ACTION:
Stimulants typically mimic the action of a class of compounds known as Trace Amines that are naturally present in the body. The canonical trace amine in the body is Phenethylamine, which forms the backbone of the vast majority of compounds in the stimulant class (as well as about a half of the ones in the psychedelic class). Trace amines typically bind to the Trace Amine Associated Receptor 1 (TAAR1) and Vesicular Monoamine Transporter 2 (VMAT2) in the pre-synaptic neuron to trigger the release of the 3 monoamines: Dopamine, Serotonin, and Norepinephrine.
Entactogens
Entactogens are a subset of Stimulants that produce strong prosocial and pro-love effects and tend to produce a far less functional and more recreational "roll" as opposed to the clearheaded and focusing "high" that raw stimulants provide. The canonical and perhaps most characteristic drug in this category is the magical MDMA.
SUBJECTIVE EFFECTS:
Intensified love, Pro-Social Behavior, Talkativeness, Stimulation, Sedation (Serotonergic compounds have a tendency to be quite sedating, which counteracts the stimulating aspects of these drugs), Emotional Enhancement, Intense Tactile Enhancement, Loss of Appetite, Insomnia, Anxiety, Anxiolysis (anti anxiety), Reduction of Fear, Psychosis, Focus Enhancement, Music Enhancement, Pro-Sexual Behavior, Horniness, Intensified Sexual Pleasure, etc
The primary difference between Entactogens and pure Stimulants is the intense feeling of love, connectedness, and well-being.
EXAMPLE DRUGS:
MDMA, 5-MAPB, 6-APB, 4-MMC, 3-MMC, 4-FMA, 4-FA, MDAI, MDPV,, MDPHP, etc
MECHANISM OF ACTION:
Entactogens tend to have very similar mechanisms of action to stimulants but with far higher ratio of serotonin release to the other 3 neurotransmitters. Serotonin's impact on the 5ht1a receptor is hypothesized to be one of the primary causes of intensified feelings of love through release of Oxytocin and its actions on the Amygdala region of the brain. Oxytocin is a compound that is known for both intensifying trust and love of those in the in-group and intensifying discrimination and distrust against the outgroup. Oxytocin is often mislabeled as the "love hormone" , but it is actually just as involved in feelings of distrust and hatred (racism, xenophobia, etc) as it is in feelings of love. Despite this, Entactogens generally have so many other euphoric and anti-anxiety effects that they typically only heighten love and connectedness rather than discriminatory feelings.
Classical Hallucinogens
A lot of the drugs on this list can produce hallucinations, but there are 3 main categories that are typically grouped together as the classical hallucinogens: Psychedelics, Dissociatives, and Deliriants. I will group these three drug classes into this category and discuss them one at a time.
Psychedelics
"Psychedelics" as a term used to describe all hallucinogens, and many still use this word in this context to this day. Over time, scientists, psychonauts, and recreational drug users alike have begun grouping hallucinogens into the 3 concrete groups I mentioned above. Psychedelics in this new context refers to the Classical Serotonergic Psychedelics. These drugs tend to induce a state of intense introspection, suppression of the Default Mode Network (DMN) that reduces our built up automated reactions, and visual hallucinations typically in the form of colorful geometric shapes and drifting and flowing movements in patterned objects.
In recent years, psychedelics' efficacy in therapy as both an aid to help patients open up during talk therapy, and as a chemical treatment to depression through its impact on neuroplasticity have slowly become more known, and a ton of ongoing research is being conducted into psychedelics use in medical treatments. They are also long term favorites of spiritual ritual participants and party goers alike.
SUBJECTIVE EFFECTS:
Anxiety, Anxiolysis (anxiety reduction), Introspection, Feelings of Unity and Connected With Others, Feelings of Unity and Connectedness to the Natural and Physical World, Body Tingles, Stimulation / Sedation (depends on the particular compound), Talkativeness, Pro-Social Behavior, Anti-Social Behavior, Geometric Visual Hallucinations, Color Enhancement, Mild to Moderate Tactile Enhancement, Visual Acuity Enhancement, Music Enhancement, Intensified Introspection, Regression to a Younger State, Novelty Enhancement, Antidepressive Effects, etc
Psychedelics are also known to have a nice "afterglow" rather than an unpleasant "comedown", which tends to boost mood and productivity for days or weeks after a strong positive trip.
Psychedelics are often combined with entactogens like MDMA, the serotonergic effects and the hallucinogenic effects of both types of compounds tend to greatly intensify the perceived profoundness of the experience while also making it far more euphoric and recreational.
EXAMPLE DRUGS:
Psilocybin (shrooms), Psilocin (active metabolite of shrooms), LSD, DMT, Mescaline, 2C-B, 2C-I, 2C-P, Other 2C-X compounds, 4-HO-MET, 5-MeO-DMT, DiPT, 5-MeO-MiPT (moxy), Methallylescaline (mal), MET, 4-HO-DET, 4-HO-MiPT, 5-MeO-MALT, 4-AcO-DMT (an inactive precursor to psilocin, similar to psilocybin "synthetic shrooms"), 4-AcO-EPT, 4-HO-DPT, 5-MeO-DALT, Al-LAD, 1p-LSD, etc
MECHANISM OF ACTION:
Psychedelics as a whole generally act on the 5ht2a receptor, which is a subset of serotonin receptors. The 5ht2a receptor is a G-Protein Coupled Receptor (GPCR) which allows for vastly complex behavior beyond simple agonism vs antagonism (see the article on pharmacodynamic basics to learn more!), and instead has numerous conformations that different compounds can pick and choose on which to activate. This allows for a unique behavior known as "biased agonism" or "functional selectivity", which psychedelics are believed to exhibit at the 5ht2a receptor. This also explains why serotonin itself rarely exhibits any hallucinogenic activity in common day to day life.
Dissociatives
Dissociatives produce a sense of disconnection and derealization, as if the world is far away or you're living in a dream. These are less well known and less popular than psychedelics, but still represent very popular hallucinogens. Dissociatives and psychedelics combined together has a very unique synergistic effect that not only takes away most of the negative side effects of both drugs but also intensifies the psychedelic trip to 11/10. Nitrous combined with psychedelics is the canonical example of this combination.
SUBJECTIVE EFFECTS:
Feeling of Disconnectedness, Dissociation, Derealization (the world feels dreamlike or unreal), Depersonalization (you yourself feels fake or dead), Loss of Pain Sensation, Loss of Tactile Sensation, Anxiolysis (anxiety reduction), Disorientation, Euphoria, Disinhibition, Loss of Motor Skills, Loss of Balance, Frame Rate Suppression (your eyes "lag"), Visual Hallucinations of Grid-like Gaps in Visual Field, Visual Hallucinations of Holes in the Visual Field, Environment Cubism / Orbism (things seem to bunch up into 3d cubes or orbs), Complete Loss of External Sensory Input (the famous K-Hole), Suppression of Fear, Emotional Suppression, Antidepressive Effects, etc
EXAMPLE DRUGS:
PCP, Ketamine, Nitrous Oxide, Xenon, O-PCE, MXiPr (3-MeO-2′-Oxo-PCiPr), DXM, FXE, MXE, DMXE, DCK, 2F-DCK, HA966, Memantine, etc
MECHANISM OF ACTION:
Dissociatives generally work by acting as antagonists of the NMDA receptor, which is a subset of glutamate receptors typically involved in learning and neuroplasticity through a process known as Long Term Potentiation (we'll get to this in a future article) or LTP, but is also heavily involved in numerous systems including the systems critical for your brain to receive external sensory data from the rest of the body. Blocking this latter system is most likely the root cause of the feelings of disconnection and dissociation along with the suppressed senses and "holes". A subsequent glutamate spike, as a response to NMDA receptors being blocked, is suggested to be the cause behind why Ketamine has strong pro-neuroplasticity effects. More research is being conducted on whether this effect holds through in other dissociatives as well.
Deliriants
Deliriants are the dark sinister cousin of the other two more light hearted style of hallucinogens, and unlike Psychedelics and Dissociatives, are inherently dangerous and harmful to both the body and the psyche.
Instead of hallucinations of complex geometric shapes or dark holes and voids, Deliriants produce fully formed realistic hallucinations that are almost impossible to tell from reality. Because of this effect, Deliriants are way more likely to cause a complete break from reality leading to potentially extremely dangerous behaviors.
Furthermore, deliriant trips are pretty much universally seen as absolutely terrifying and dysphoric, having pretty much 0 recreational value whatsoever, except for rare individuals who manage to get some antidepressive effects from them. Deliriants are also universally very straining on the body, essentially risking early onset dementia and permanent loss of cognitive abilities with each trip.
The subjective experience itself is also quite traumatizing, with fully formed visual and tactile hallucinations of spiders crawling all over, shadow people, hatman, talking to people who aren't there, sinister auditory hallucinations (similar to psychosis), visuals of writhing guts and other uncomfortable imagery, and various other delirious beliefs. At high enough dosages, total delirium is expected, characterized by a total disconnection from reality.
Although this class of drugs produces perhaps the most unique and fascinating hallucinogenic experiences out of all drug classes, trying them is HIGHLY DISCOURAGED and represents immense risk to both physical and mental health.
Datura Flower - The seeds of this plant contain Atropine, Scopolamine, and Hyoscyamine. Perhaps one of the most well known natural Deliriants, and a notorious historical poison.SUBJECTIVE EFFECTS:
Fear, Panic, Terror, Anxiety, Sense of Impending Doom, Polyuria (excessive need to pee), Difficulty Urinating, Fully Formed Visual Hallucinations, Fully Formed Tactile Hallucinations, Fully Formed Auditory Hallucinations, Disconnection from Reality, Delirium, Dementia Risk, Seizure Risk, Tachycardia, Visual and Tactile Hallucination of Insects Crawling over Skin.
EXAMPLE DRUGS:
Diphenhydramine (DPH / Benadryl), Doxylamine, Dimenhydrinate (Dramamine), Atropine, Scopolamine, Hyoscyamine, Datura, Belladonna, Deadly Nightshade, Benzydamine, etc
MECHANISM OF ACTION:
Classical Deliriants impart their unique actions by being antagonists at the Muscarinic Acetylcholine (mACH) receptors. Blocking mACH is known to cause both delirium and also the uncomfortable physical side effects.
Lowered levels of acetylcholine is also heavily implicated in Alzheimer's and other types of diseases that are correlated with Dementia. Prolonged usage of these substances lead to acetylcholine dysregulation and a far heightened risk of developing early onset dementia.
Cannabinoids
Cannabinoids are a class of drug that is perhaps one of the more well known recreational substances out there (other than alcohol and caffeine) and is primarily exemplified by delta-9-THC, the primary psychoactive compound in the marijuana plant.
Over time, we've discovered countless minor cannabinoids that are contained in the marijuana plant which all contribute to the "entourage" effect of what weed feels like. Some of these "alt cannabinoids" include examples such as Delta 8-THCV, Delta 9-THCV, Delta 8-THC, Delta 8-THCP, Delta 9-THCP, Delta 8-HHC, Delta 9-HHC, and numerous others.
Synthetic cb1 full agonists represent immense psychosis risk and usage is heavily discouraged.
We've also synthesized numerous synthetic cannabinoids, typically with strong fully agonist activity at the cb1 receptor. Compared to most phytocannabinoids (plant derived cannabinoids), which have only partial agonism or antagonism at the cb1 receptor, these full agonists tend to produce a much more intense high which is far more prone to psychosis risk than normal weed. The working hypothesis here is that the cb1 receptor has a close relationship with mesolimbic dopamine release, which is strongly correlated with psychosis. Although normal weed represents a nonexistent psychosis risk to those who are not predisposed to it, for those who are genetically predisposed, cannabinoids represents the drug category with the single highest risk of drug induced psychosis (DIP).
SUBJECTIVE EFFECTS:
Relaxation, Anxiolysis (reduction of anxiety), Anxiogenesis (increase of anxiety), Euphoria, Novelty Enhancement, Mild Stimulation, Sedation, Somnolence (sleepiness), Loss of Motivation, Focus Enhancement, Time Dilation (time slows down), Thought Deceleration, Muscle Relaxation, Sensation Enhancement, Mild Analgesia (pain relief), Sociability Increase, Sociability Decrease (these effects are dosage dependent), etc
EXAMPLE DRUGS:
Delta 9-THC, Delta 8-THC, Delta 8-THCV, Delta 9-THCV, Delta 8-THC, Delta 8-THCP, Delta 9-THCP, Delta 8-HHC, Delta 9-HHC, CBD, H4CBD, Delta 8-THCO, Delta 9-THCO, Spice, K2, tetrahydromagnolol, etc
MECHANISM OF ACTION:
Cannabinoids impact their effects through binding to the cb1 and cb2 cannabinoid receptors. Most psychoactive compounds found in the weed plant are cb1 and cb2 partial agonists, with some synthetic cannabinoids being cb1 full agonists. There's also a series of compounds in the weed plant, such as CBD, THCV, and H4CBD, which have shown far weaker intrinsic activity at cb1, and might even be antagonists. These tend to balance out the anxiety inducing and psychosis inducing effects of THC and other cb1 agonists and reduces the risk of cannabinoid usage.
Opioids
Opioids are named after the Opium poppy (Papaver somniferum) and is one of the most euphoric and addicting category of drugs. These substances are typically broken down into two subcategories: Opiates, those derived directly from the Opium poppy; and synthetic Opioids. These drugs are primarily known for their analgesic (pain relieving) properties, but their intensely euphoric highs make them very popular recreational drugs.
More unique amongst drugs that target the opioid receptors are Kappa Opioid Receptor (KOR) agonists such as salvia. These drugs induce extremely powerful and dysphoric hallucinogenic states that are some of the most profound amongst all drugs (even more so than deliriants).
SUBJECTIVE EFFECTS:
Analgesia (pain-relief), Euphoria, Relaxation, Anxiolysis (reduction of anxiety), Sedation, Somnolence (sleepiness), Nausea, Emesis (vomiting), Respiratory Depression, Muscle Relaxation, Itchiness, Focus Enhancement, Novelty Enhancement, Immersion Enhancement, Irritability, etc
EXAMPLE DRUGS:
Heroin, Opium, Tramadol, O-DSMT, Kratom, Oxycodone, Hydrocodone, U-47700, Fentanyl, Carfentanyl, Tianeptine, etc
Dysdelics:
Hallucinogenic KOR agonists provide vastly different subjective experiences from analgesic opioids and are listed separately here:
Salvia (Salvinornin A), Salvinorin B methoxymethyl ether, etc
MECHANISM OF ACTION:
Most analgesic opioids are agonists at the Mu and Delta opioid receptors, both of which play a major role in the signaling pathways for pain. Mu and Delta opioid receptors are also implicated in the hedonic hotspots, leading to sensations of consummatory pleasure. The Kappa Opioid Receptors are typically bound to by the endogenous Dynorphin, which tends to produce dysphoric, uncomfortable experiences. The Kappa Opioid Receptor and dynorphin are implicated in the subjectively negative experiences involved in psychological withdrawal, and this is probably one of the causes for the amount of discomfort and dysphoria that KOR agonists like salvia can produce.
Gabanergic Depressants
Ahh Alcohol, the first invention of settled humanity and man’s second best friend; the cause of and solution to all of life’s problems. Ethanol is one of the oldest psychoactive compounds known to man and has had a deeply intertwined and profound relationship with the story of our species. Today it is still the second most widely used psychoactive compound worldwide, second only to caffeine.
Alcohol belongs in a group of drugs known as Gabanergic Depressants, and impacts its effects primarily through activity on the Gaba system. (Though alcohol itself also has a decent amount of dissociative and stimulating effects as well).
This drug class is primarily exemplified by anxiolysis (anxiety reduction), sedation, and disinhibition; thus making them well sought after treatments for anxiety disorders and insomnia. The biggest drawback of this drug class is that Gabanergic compounds are highly addicting and typically present with potentially fatal withdrawals if quit abruptly. Care should be taken to avoid building up a dependence, and in the unfortunate case of addiction a proper taper should be employed to avoid potentially deadly withdrawal symptoms rather than quitting cold turkey.
Note: Due to the subjective effects of Gaba B agonism being more similar to gabapentinoids I will discuss them in the following section instead.
SUBJECTIVE EFFECTS:
Anxiolysis (anxiety relief), Euphoria, Pro-social Behavior, Emotional Enhancement, Disinhibition, Talkativeness, Sedation, Somnolence (sleepiness), Nausea, Memory Inhibition, Thought Deceleration, Visual Acuity Suppression, Music Enhancement, Confidence, Recklessness, “Drunkeness”, Irritability, etc
EXAMPLE DRUGS:
Drinking Alcohol (Ethanol), 2-methyl-2-butanol, Alprazolam (Xanax), Clonazepam (Klonopin), Clonazelam, Etizolam, Bromazolam, Lorazepam (Ativan), Zolpidem (Ambien), Zopiclone, Pentobarbital, Secobarbital, Carisoprodol (Soma), Meprobamate, etc
MECHANISM OF ACTION:
Gaba is the most prolific inhibitory neurotransmitter and most Gabanergic Depressants produce their effects by being either agonists at the Gaba A Receptors or being positive allosteric modulators (PAMs) at the Gaba A receptors. (We will discuss Gaba B agonists below).
Gabapentinoids and Gaba B Agonists
A lesser known drug class, Gabapentinoids and Gaba B Agonists share a lot of the same effects as Gabanergic Depressants, but tend to be far more clearheaded and productive. These drugs tend to produce an intensely euphoric and extremely social experience while still having very strong control of your cognitive abilities. You can still go about your day without any interruption and almost every activity is still possible, and in fact may seem far easier, on these substances.
Gabapentinoids reliably bring about the experience of a perfect 10/10 day and will have you talking to every person you meet with the confidence of James Bond while you feel more productive, happier, less anxious, more chatty, more confident, and more hopeful than you at your finest. These drugs are probably the closest you can get to NZT or Felix Felicis, and would be the perfect compound if not for their biggest glaring drawback: Extremely high addiction risk and potentially fatal withdrawals just like gabanergic depressants. These substances are even more insidious than Gabanergics, because they leave you so functional and the effects are so easy to hide that it is a much harder temptation to resist.
Gabapentinoids and Gaba B agonists do differ in effects in a lot of ways, but the difference is inconsistent from individual to individual, and the two classes share enough similarities that I am grouping them together into one section here.
This drug class is named after Gabapentin.
Phenibut will give you the "social confidence of James Bond" according to many of its usersSUBJECTIVE EFFECTS:
Anxiolysis (anxiety relief), Euphoria, Pro-social Behavior, Emotional Enhancement, Disinhibition, Talkativeness, Sedation, Somnolence (sleepiness), Nausea, Thought Acceleration, Thought Deceleration, Extreme Talkativeness, Music Enhancement, Extreme Confidence, Mild Recklessness, Focus Enhancement, Time Compression (time speeds up), Motivation Enhancement, Mood Boost, Irritability, etc
EXAMPLE DRUGS:
Gabapentin, Pregabalin, Phenibut, F-Phenibut, Baclofen (Not very CNS active unlike others in this list), Mirogablin, etc
MECHANISM OF ACTION:
Gabapentinoids are Voltage Gated Calcium Channel inhibitors, they block these presynaptic channels which has the effect of reducing the overall volume of monoamine released.
Gaba B agonists work by binding to Gaba B receptors as agonists.
This about covers most of the major drug classes. There are countless more minor classes that we might get to in future articles!
