What really goes on when you're on?

Mushrooms and cocaine and weed, oh my! What’s happening in a brain under the influence, and what causes highs and hallucinations – and the corresponding crashes and withdrawal?

Illustration by Olivia Baenziger

Illustration by Olivia Baenziger

When we eat food, we like to think we know what’s going on with our bodies. Get hungry, eat food, get full, digest, poop it out. Rinse and repeat, nothing to write home about. However, taking drugs can introduce a whole other realm of biological experiences. Tingles, trippy, nippy – physical and emotional alterations are what you expect when you take illicit drugs.

But do we know what’s really happening during our psychedelic benders? Why do we feel the way we do when we take drugs, what’s in them and what are they doing to us? To exercise caution when experimenting with drugs means to be aware of and prepared for the risks involved with taking mind-altering chemicals. Here’s a primer on what happens when you take some of the more common illicit drugs.


Marijuana is among the most popular illicit drugs. Most people try marijuana before trying other drugs, and this is presumably why it’s been labelled ‘the gateway drug’. The main psychoactive part of marijuana is tetrahydracannibinol (THC), which resembles a cannabinoid naturally produced in our brains called anandamine. This naturally occurring molecule helps regulate our mood, sleep, memory and appetite. 

Marijuana affects pain modulation and can give a sense of euphoria.     Katherine Hitt/Flickr    (CC BY-ND 2.0)

Marijuana affects pain modulation and can give a sense of euphoria. Katherine Hitt/Flickr (CC BY-ND 2.0)


THC has been found to affect two cannabinoid receptors: CB1, mostly found in the brain, and CB2, found in peripheral tissues. By binding to the CB1 receptor, THC increases dopamine and norepinephrine release, affecting pain modulation and giving a sense of euphoria and relaxation. It also generally enhances experiences, whether negative or positive, and can often cause anxiety. Brain regions with cannabinoid receptors are involved in short-term memory, learning, coordination, movement control and higher cognitive functions, and these are related to the effects of marijuana use.

Crack cocaine

Crack! It gets its name from the sound it makes when heated. Crack is a form of cocaine, a drug that is extracted from the leaves of a coca plant. When you add a weak base, such as baking soda, to the powdered form of cocaine, the composition is altered and it forms the ‘rocks’ known as crack cocaine. The rocks have a higher melting point (190C) than cocaine (90C), allowing it to be smoked, which delivers it to the brain in a mind-bendingly fast eight seconds. Snorted cocaine takes a relatively sluggish three minutes to reach the brain. However, once they get there, crack and cocaine are the same to the brain.

Cocaine has similar behavioural and physiological effects as methamphetamine. It releases large amounts of dopamine, giving energy, alertness, and heightened awareness of senses. However, crack does something a little bit different. When dopamine is released, it binds to neurons and triggers the feelings of euphoria, and then is usually reabsorbed by a dopamine transporter. However, crack alters this process by attaching to the transporter and blocking dopamine reuptake, so that dopamine continues to build up and up… but only for about 10 minutes. After that, crack is metabolised and as a result, dopamine levels plummet, giving intense feelings of depression. 

It takes the body a while to replenish all the dopamine, which is why this drug is so addictive: users feel the need to reach that high again and again and again. This dopamine crash causes irritability, restlessness and paranoia. It can also lead to delusional parasitosis, which is the uncomfortable feeling that bugs are crawling around under your skin. This sensation can result in self-destructive behaviour as the person attempts to eradicate these bugs by any means possible. Crack can also cause fatalities due to heart attacks or stroke. There’s a reason people say crack is whack.

Lysergic acid diethylamine (LSD)

Like marijuana, this drug has its own day – Bicycle Day – which falls on April 19. LSD was created by Albert Hoffman. After “experimenting” on himself, Hoffman believed he had made himself ill so he cycled home from his lab (don’t drug and drive, kids). Following his experiences with LSD, Hoffman became dedicated to studying mind-altering drugs, hoping they would make a contribution to psychiatry.

Because it affects the visual cortex,     LSD can cause visual hallucinations.     Kittykatfish/Flickr    (CC BY-NC 2.0)

Because it affects the visual cortex, LSD can cause visual hallucinations. Kittykatfish/Flickr (CC BY-NC 2.0)


Time can feel extremely slow on LSD, and you may have visual hallucinations. Acid, as it’s also called, affects dopamine, serotonin and adrenergic (noradrenaline and adrenaline) receptors. Serotonin is key for hallucinations, as the receptor that makes us hallucinate is a serotonin receptor called 5-HT2A, which plays a massive role in the visual cortex. Professor Jack D Cowan, a mathematical biologist, said that kaleidoscopic hallucinations could be an innate mental response because the brain tends to create patterns when it is unstable. He has also developed mathematical models of hallucination.

Experiences on LSD can be extremely subjective, relying heavily on environment and mood. The physical effects, however, are quite objective and include dilated pupils, sweating or chills, dry mouth, sleeplessness, a change in body temperature, and tremors. This is due to the brain mistakenly perceiving a threat because of the rapidity of the change in sensation. Author Terence McKenna mentioned that hunter-gatherer tribes could have taken psychedelics in order to become hyper-aware. The mental effects of LSD can include fear, distorted perception and visuals, uncontrollable laughter, a sense of unity with nature, and euphoria.

Magic mushrooms

The main active ingredient in shrooms is psilocybin. When ingested, it is broken down into the drug psilocin, which then goes on a journey to the brain. Psilocin has a similar chemical structure to serotonin, allowing it to bind to serotonin’s receptors and prevent its reuptake, causing you to perceive things without a physical stimulus. These perceptions are hallucinations that can include visions, sounds, thoughts or feelings. They can be divinely spiritual and insightful, or completely horrible, causing fear, anxiety and paranoia.

There are dramatic differences in communication between brain networks in people given either (a) a non-psychedelic compound or (b) psilocybin (the pro-drug form of psilocin).   Petri et al., 2014  (CC BY 4.0)

There are dramatic differences in communication between brain networks in people given either (a) a non-psychedelic compound or (b) psilocybin (the pro-drug form of psilocin). Petri et al., 2014 (CC BY 4.0)


The effects of shrooms generally last three to eight hours, but as they alter your sense of time, it can feel much longer. Psilocin causes activation of the hippocampus and anterior cingulate cortex of the brain, which are both associated with dreaming and putting your mind in a sort of ‘waking dream’ state. The myriad physical sensations associated with shrooms include nausea, muscle relaxation, twitching, drowsiness, a light or heavy perception of your body, pupil dilation, lack of coordination, increased temperature, heart rate and blood pressure, and numbness or tongue, lips or mouth. Psychologically, you might experience heightened senses and perceptions, synaesthesia, a sense of detachment, impaired judgement, feelings of unity and tension, anxiety and restlessness.


Opiates are chemicals derived from the opium poppy, and they include pain-killing drugs like heroin and morphine. While opiates are naturally occurring, opioids such as codeine and oxycodone are man-made. However, they have the same effects on us. Once ingested, heroin is converted to morphine. It dulls pain by binding to opiate receptors in the body, triggers sensations of pain relief, and brings about a massive surge of dopamine. Users adjust and build tolerance to heroin, as pain thresholds are lowered and sensitivity to pain signalling is amplified. These pain-signalling pathways can become overactive, resulting in the feeling of needing more heroin just to feel normal.

A dry mouth, warm and flushed skin, heavy limbs and clouded mental functioning are some of the bodily sensations associated with heroin use. Following this initial euphoria, the user enters a drowsy state, colloquially referred to as ‘on the nod’. The withdrawal symptoms occur about eight to 12 hours after use. Eyes begin to water and the user experiences flu-like symptoms: sneezing, weakness, vomiting, muscle cramps, nausea, diarrhoea, and depression due to lowered dopamine levels. These symptoms increase in severity over two to three days, and are gone within 10 days. The muscle spasms in legs produce kicking movements, as the users ‘kick the habit’.



While humans have been experimenting with drugs for millennia, most scientific experiments on the effects of drugs are fairly recent. These kinds of studies explain drugs’ mechanisms, revealing what they do to us biologically. This new knowledge is beneficial, although even being well informed might not deter the curious or bored. In fact, knowing more might encourage some people. In the meantime, researchers will keep observing intoxicated study participants and maybe go on some bicycle rides of their own. 

Edited by Ena Music, and supported by Nathan Dannatt.