What drugs do to the brain

Step 1 · The way inSwallowed as root bark, given in steps through the night. The liver, mainly through the enzyme CYP2D6, turns ibogaine into noribogaine, and both reach the brain.

Step 2 · The target, up closeNot one target but several: NMDA receptors, kappa opioid receptors and the serotonin transporter (SERT), among others.

Step 3 · The brain duringNo brain scan has ever been taken during an iboga night, so the map stays blank. The only recordings made during the acute effects are two 30-minute EEGs from 1999, in a small report of five people given ibogaine: the traces looked normal, awake or drowsy, with no sign of seizure activity (Luciano et al., 1999). Guests describe a long, lucid review of their own life, with the body heavy and still.

Step 4 · How long it lastsThe ceremony runs until sunrise, about twelve hours, then a day of processing. Noribogaine leaves slowly, with a half-life of 28 to 49 hours (Glue et al., 2015), one reason the heart is watched after the night.

Step 1 · The way inSwallowed as capsules of purified ibogaine. The liver turns it into noribogaine through CYP2D6, and how active that enzyme is changes how much ibogaine builds up in the blood and how long it stays (Glue et al., 2015).

Step 2 · The target, up closeThe same molecule, so the same targets: NMDA receptors, kappa opioid receptors, the serotonin transporter and others. What differs from the root is the dose form, the setting and the absence of the bark's other alkaloids.

Step 3 · The brain duringEvery modern imaging study records the brain before and after the session, never during it, so what the brain does in those hours is still unmapped in people. In rats, acute ibogaine changes gamma rhythms and produces REM-like brain traits while the animal is awake (González et al., 2021). People describe a dream-like phase of memories and images in the first hours, then a long, reflective phase.

Step 4 · How long it lastsIn veterans recorded about three and a half days after magnesium-ibogaine treatment, brain waves had shifted toward slower theta and alpha rhythms, and the shift tracked better self-control on tests (Lissemore et al., 2025).

Step 1 · The way inSwallowed, psilocybin is turned into psilocin, the form that acts in the brain. Effects usually begin within the first hour.

Step 2 · The target, up closePsilocin works mainly on serotonin 5-HT2A receptors, the same main target as LSD and DMT.

Step 3 · The brain duringIn brain scans, psilocybin lowered blood flow and activity in the hubs of the default mode network and in the thalamus, and the bigger the drop in the front of the brain, the stronger the experience felt (Carhart-Harris et al., 2012, who gave it intravenously).

Step 4 · How long it lastsThe effects last about four to six hours. In depression trials, brain networks were more integrated after psilocybin therapy, and the change tracked improvement (Daws et al., 2022).

Step 1 · The way inSwallowed. Effects begin within about an hour.

Step 2 · The target, up closeLSD works mainly on 5-HT2A receptors. A crystal structure of LSD bound to a closely related serotonin receptor, with computer simulations, suggested part of the receptor closes like a lid over the molecule, which may help explain why its effects last so long (Wacker et al., 2017).

Step 3 · The brain duringIn brain scans, the visual cortex became more connected with the rest of the brain, tracking the visions, while the default mode network lost coherence, tracking the dissolution of the sense of self (Carhart-Harris et al., 2016).

Step 4 · How long it lastsEffects last up to about twelve hours, and LSD's half-life in the blood was about two and a half hours (Dolder et al., 2017).

Step 1 · The way inSwallowed alone, DMT is broken down in the gut by monoamine oxidase (MAO). The vine's harmala alkaloids block MAO, so the DMT gets through to the brain.

Step 2 · The target, up closeDMT works mainly on serotonin 5-HT2A receptors.

Step 3 · The brain duringIn brain scans, the visual cortex lit up while people imagined images with their eyes closed, close to the level of real seeing (de Araujo et al., 2012), and the default mode network went quieter (Palhano-Fontes et al., 2015).

Step 4 · How long it lastsEffects peak at one and a half to two hours (Riba et al., 2003) and generally pass within about four. Because of the MAO block, ayahuasca can interact dangerously with antidepressants.

Step 1 · The way inInhaled, it reaches the brain through the lungs within seconds. The body breaks it down quickly, mainly through the enzyme MAO-A.

Step 2 · The target, up closeIt acts on serotonin receptors, with a stronger pull on 5-HT1A than on 5-HT2A, unlike most classic psychedelics (Reckweg et al., 2022).

Step 3 · The brain duringBrain imaging during 5-MeO-DMT is still scarce, so the map stays blank. People describe an intense, brief dissolution of the sense of self, often with little visual imagery.

Step 4 · How long it lastsInhaled, the main effects last about fifteen to twenty minutes (Reckweg et al., 2022). Combining it with an MAO inhibitor, such as ayahuasca’s vine, is considered dangerous.

Step 1 · The way inSwallowed. Effects begin within about an hour.

Step 2 · The target, up closeMDMA enters neurons through the serotonin transporter (SERT) and runs it in reverse, pushing serotonin out into the gap, with smaller releases of noradrenaline and dopamine.

Step 3 · The brain duringIn brain scans, blood flow fell in the right medial temporal lobe, including the amygdala and hippocampus, and the front of the brain became less connected with those regions (Carhart-Harris et al., 2015).

Step 4 · How long it lastsMain effects last about three to six hours. Some people describe low mood in the days after. Overheating and drinking too much water are among its acute dangers.

Step 1 · The way inUsed medically as an infusion or a nasal spray. It reaches the brain within minutes.

Step 2 · The target, up closeKetamine slips into the channel of the NMDA receptor and plugs it, blocking a main route of glutamate, the brain's chief excitatory messenger.

Step 3 · The brain duringNMDA receptors are spread across the brain, densely in the cortex and hippocampus. People describe feeling detached from their body and surroundings.

Step 4 · How long it lastsMain effects pass within about an hour. In a trial for treatment-resistant depression, one infusion lifted mood within hours, and in about a third the effect lasted at least a week (Zarate et al., 2006). Frequent heavy use can damage the bladder.

Step 1 · The way inInhaled, THC reaches the brain within minutes. Eaten, it passes through the liver, which turns it into 11-hydroxy-THC, so effects come later and last longer.

Step 2 · The target, up closeTHC switches on CB1 receptors. They sit on the sending side of the synapse and turn down how much messenger the neuron releases.

Step 3 · The brain duringCB1 receptors are densest in the basal ganglia, the hippocampus and the cerebellum (Herkenham et al., 1990), areas for movement, memory and coordination, which fits the effects on short-term memory and coordination.

Step 4 · How long it lastsSmoked, effects last about two to four hours; eaten, longer. THC is stored in body fat, so in daily users it can be detected for weeks.

Step 1 · The way inThrough the lining of the nose it reaches the brain within minutes; inhaled forms arrive faster.

Step 2 · The target, up closeCocaine blocks the dopamine transporter (DAT), the pump that clears dopamine after a signal, so dopamine builds up between neurons. People felt the high once about half of the transporters were blocked (Volkow et al., 1997).

Step 3 · The brain duringThe build-up is strongest in the striatum, the core of the brain's reward circuit.

Step 4 · How long it lastsSnorted, the high lasts roughly fifteen to thirty minutes, then a crash and craving. People who used cocaine heavily had fewer dopamine D2 receptors in the striatum, linked to lower activity in the front of the brain, and the deficit persisted three to four months after detox (Volkow et al., 1993).

Step 1 · The way inBoth pass easily from the blood into the brain.

Step 2 · The target, up closeAmphetamines enter neurons through the dopamine and noradrenaline transporters and run them in reverse, pushing dopamine out rather than only blocking its return.

Step 3 · The brain duringDopamine floods the striatum, the reward circuit, for hours rather than minutes.

Step 4 · How long it lastsMethamphetamine's effects last many hours. In five people who had used it heavily, dopamine transporters were reduced and partly recovered after about a year or more without the drug (Volkow et al., 2001).

Step 1 · The way inInhaled, nicotine reaches the brain within seconds of each puff.

Step 2 · The target, up closeIt switches on nicotinic acetylcholine receptors, especially the α4β2 type, on the neurons that release dopamine.

Step 3 · The brain duringDopamine is released in the reward circuit within seconds of inhaling, which ties the habit to the act of smoking (Benowitz, 2009).

Step 4 · How long it lastsNicotine's half-life is about two hours, so cravings return within hours. Regular use leaves the brain with more nicotinic receptors than before (Benowitz, 2009).

Step 1 · The way inOpioids reach the brain within seconds when injected or smoked, and more slowly when swallowed.

Step 2 · The target, up closeThey switch on mu opioid receptors, the brain's own pain and reward switches, normally used by endorphins.

Step 3 · The brain duringIn the reward circuit they raise dopamine; in the brainstem they slow the drive to breathe (Pattinson, 2008), which is what makes an overdose deadly.

Step 4 · How long it lastsShort-acting opioids wear off in a few hours. After daily use, withdrawal follows, with aching, sweating, diarrhea and strong craving. Tolerance falls quickly after stopping, so a former dose can kill.

Step 1 · The way inAbsorbed from the gut. Its main alkaloid is mitragynine.

Step 2 · The target, up closeMitragynine is a partial agonist at mu opioid receptors: it switches them on, but only partly, about a third of the maximum response in cell tests (Kruegel et al., 2016).

Step 3 · The brain duringIt works on the same opioid circuits as other opioids. Low doses are described as stimulating, higher ones as sedating.

Step 4 · How long it lastsEffects last a few hours. Daily use can lead to dependence, and stopping brings a withdrawal that resembles a milder opioid withdrawal.

Step 1 · The way inAbsorbed from the stomach and gut into the blood, reaching the brain within minutes. The liver clears it at a roughly fixed rate.

Step 2 · The target, up closeAlcohol strengthens GABA-A receptors, the brain's main brake, and weakens NMDA glutamate receptors, its main accelerator.

Step 3 · The brain duringIt releases dopamine in the reward circuit (Boileau et al., 2003) while dulling the cerebellum, which handles balance, and the front of the brain, which handles judgment.

Step 4 · How long it lastsEffects last as long as alcohol stays in the blood, hours. In people who are dependent, stopping suddenly can cause dangerous withdrawal with tremor, seizures and delirium, so detox needs medical care.

Step 1 · The way inTaken as pills; some act within half an hour.

Step 2 · The target, up closeBenzodiazepines attach to a side site of the GABA-A receptor and make it respond more strongly to GABA, the brain's main calming messenger (Griffin et al., 2013).

Step 3 · The brain duringGABA-A receptors are found throughout the brain, so activity is damped broadly: anxiety eases, muscles relax, sleepiness rises.

Step 4 · How long it lastsSome last hours, others, like diazepam, days. After regular use, stopping suddenly can trigger seizures, so tapering under medical care is needed. With opioids or alcohol, breathing can stop.