Answer by Jens Mowatt:

The answer to your question depends on your drug of choice. The word “high” is used for a wide variety of psychoactive substances.

Different substances affect the brain in different ways, but they all have something in common: they affect neurotransmitters in the brain. Neurotransmitters are used for normal “communication” between neurons. Whenever the normal activity of these molecules is is disrupted by a substance, there is a possibility for a euphoric feeling we call a “high”.

Thus, when someone is “high”, the brain is functioning differently than it normally is. The mechanisms behind this depend on which drug you decide to ingest.


Yohan John has eloquently described how marijuana affects the brain: it does so by mimicking the action of endogenous cannabinoids in the brain. The THC in cannabis has a similar structure to 2-AG and anandamide, which allows it to bind their receptors.

Where a receptor is located in the brain matters. The main receptor that THC binds to, CB1, is found just about everywhere in the brain:

  • Cerebral Cortex – By binding here, cannabis exerts its effects on your executive functions. Things like reasoning, judgement and memory are affected when THC binds to this area.
  • Hippocampus – This is an area of the brain implicated in consolidating memories. It is thought that cannabis interferes with this function, inhibiting the conversion of short-term memory into long-term memory.
  • Basal Ganglia and cerebellum – Because these areas regulate motor learning and movement, it is thought that cannabinoid binding here is responsible for the motor impairments while you are high.

As you can see, the function of a drug depends on what area of the brain it binds to. And the area that a drug binds to depends on the location of receptors that it has an affinity for.


One of the most popular recreational drugs is cocaine, also known as “crack” when it is in its freebase form. When you snort, smoke or inject this drug, you experience a “high” that is far more intense than marijuana. While cannabis is an analgesic, hallucinogen and depressant, cocaine is a powerful stimulant.

Like cannabis, cocaine alters neurotransmitter function in the brain. But it does so by affecting different neurotransmitters: the monoamines. These include norepinephrine, serotonin, and dopamine; although it affects all of these, dopamine is thought to be mainly responsible for the euphoric feelings of the drug.

Cocaine does this by binding to the dopamine transporter (a protein that “transports” dopamine from the synapse into a neuron’s axon terminal so it can be recycled). By doing so, this leaves more dopamine in the synapse than there normally would. It highjacks your dopaminergic system.

(Photo taken from Psychopharmacology: Drugs, the brain and behaviour; Meyer & Quenzer)

As a result, your mesolimbic and nigrostriatal dopamine pathways experience a boost in dopamine transmission.

  • Mesolimbic pathway – This projects from the ventral tegmental area (VTA) to the nucleus accumbens (Nacc) in the limbic system. It is thought this is responsible for the reinforcing effects of the drug, as well as the euphoria.
  • Nigrostriatal pathway – This dopamine pathway starts in the substantia nigra and projects to the striatum. It is thought to be involved in motor movements. In fact, people with parkinsons disease have decreased dopamine transmission in this pathway, resulting in impaired motor movements. However, dopamine has the reverse effect, increasing dopamine levels. This could be responsible for the locomotor (unable to stop moving) and stereotype (doing repetitive movements) effects seen in cocaine users.


Another common drug that gives people a “high” is heroin. It is a semi-synthetic opiate based on the chemical structure of morphine, but it has an extra acetyl group. At the blood brain barrier it is converted into morphine. So what we are really looking at is the effect morphine has on the brain.

In the brain there are endogenous opioids, just like there are endogenous cannabinoids. These include endorphins, endomorphins, enkephalins and others. Overall, these substances are highly implicated in analgesia (removing pain). Morphine has a similar structure, and thus can bind to the same receptors, mimicking the effects of endogenous opioids.

There are various functions that are affected:

  • Pain regulation – Morphine binds to the delta and mu-opioid receptors, activating the descending pain-regulation pathways. This ensures that the pain signals from the spinal cord don’t reach the brain. Not only does morphine block immediate pain, it also blocks late pain by acting on the anterior cingulate cortex (ACC). This numbs any emotional pain the user may have, and is part of why it is so attractive to users.
  • Inhibition of GABA – GABA is an inhibitory neurotransmitter, decreasing the likelihood the post-synaptic neuron will fire. It keeps the dopamine system in check, making sure too much dopamine does get released from the VTA to the NAcc. However, binding to opioid receptors on GABA cells inhibits this inhibition, leading to an increase in dopamine release in the nucleus accumbens. This is part of the euphoria and strong reinforcement users experience.

(Photo taken from Psychopharmacology: Drugs, the brain and behaviour; Meyer & Quenzer)

Normally the task of inhibiting GABA is performed by endogenous beta-endorphin, but morphine highjacks those same receptors, having an effect that is far more intense.

To summarize…

Your brain functions differently than normal while you’re on drugs. The euphoric “high” you experience while on drugs depends on the neurotransmitter system that is being affected. Marijuana, cocaine, heroin and other psychoactive substances all in some way alter neurotransmitter function, and by doing so they alter brain function.

How does the brain function when a person is high?