Drugs, Brain and Behaviour (17) - Hallucinogens

Hallucinogens

Drugs that alter perception, thought, and mood, producing hallucinations (perceptions without external stimuli).

Main types of Hallucinogens

• Psychedelics

• Dissociatives

• Deliriants

Psychedelics

Substances that change or enhance:

• Sensory perceptions

• Thought processes

• Energy levels

Effects of Psychedelics

• Visual hallucinations

• Altered sense of time

• Intensified emotions

• Altered Thought processes

• Synesthesia (mixing of senses)

Dissociatives

Substances that produce detachment from reality and out‑of‑body experiences (e.g. PCP and ketamine).

Deliriants

Substances that cause confusion, delirium, and anticholinergic effects.

Indolealkylamines

(Mostly) Natural, short‑acting psychedelics structurally similar to serotonin. (e.g. LSD and Psilocybin).

Phenylethylamines

Psychedelics structurally similar to dopamine and norepinephrine → mixed stimulant + hallucinogenic effects (e.g. Mescaline and MDMA).

LSD

Synthetic Indolealkylamine hallucinogen taken via blotter paper or liquid. Contains lysergic acid, which causes:

• Vasoconstriction

• Convulsions

• Excitement

• Hallucinations

History of LSD

• 1938 synthesised

• 1943 first ingested by Hoffman

• 1953–64 Used in MK‑Ultra

• 1965 restrictions

• 1967 Schedule I drug

Effects of LSD

• Visual Hallucinations

• Altered time

• Intensified emotions

• Synesthesia

• Cognitive changes.

Adverse effects of LSD

• Psychosis

• Flashbacks

• HPPD

Psilocybin

“Magic Mushrooms” Indolealkylamine Psychedelic with similar effects to LSD but shorter‑lasting.

Mescaline

Natural Phenylethylamine found in peyote cactus, ingested fresh or powder, similar effects to LSD:

• Vivid colours

• Spiritual insight

• Kaleidoscopic visions

MDMA

Synthetic Phenylethylamine structurally resembling amphetamines → stimulant & hallucinogenic effects. (“Ecstasy”)

MDMA & Self-Administration

Readily self-administered by rats.

MDMA dose and duration

• 50–150mg

• lasts 5–6 hours

Effects of MDMA

• Euphoria

• Empathy

• Energy

• Enhanced sensory perception

Adverse Effects of MDMA

• Depression

• Anxiety

• Concentration problems; worse with frequent use.

MDMA Mechanism of Action

Indirect serotonergic agonist; enters via SERT and promotes serotonin release.

History of MDMA

• 1912 synthesised

• Shulgin reinvents

• 1978 Human studies

• 1985 Schedule I drug

• 1990s rave use

5‑HT2A receptor

Main (Excitatory) Receptor where psychedelics act as agonists, especially in cortex.

5‑HT1A receptor

Inhibitory Receptor where psychedelics act as agonists especially in Raphe. But this is NOT responsible for hallucinogenic effects.

Effect of blocking 5‑HT2A receptor

Hallucinogen-evoked Behaviours are reduced/eliminated following 5‑HT2A antagonists or gene knockout (e.g. “wet dog shake” in mice)

Effect of Psychedelics on cortical activity

Increased sensory cortex activity and disrupted information filtering.

Set and Setting

• Set: Mindset and expectations

• Setting: Environment and context

They strongly influence whether a “trip” is positive or negative.

Tolerance to Psychedelics

Develops rapidly with repeated use.

Dependence of Psychedelics

Very low physical dependence and withdrawal symptoms

Risks for Hallucinogens

• Accidents: Impaired judgement → risky behaviour.

• Psychological Harm: Bad trips, anxiety, panic, HPPD.

Who is most vulnerable to hallucinogen risks?

Individuals predisposed to psychosis