Psychedelics & Hallucinogenics: Detailed Lecture Slides

Psychodelics & Hallucinogenics Part 2 MDMA (Ecstasy) MDMA (Ecstasy) 3,4-Methylenedioxymethamphetamine (MDMA) is a mixed stimulant-psychedelic drug! Schedule 1 drug Street names: Ecstasy, Molly, XTC, E, X, Beans, disco biscuit, and Adams. Discovered in 1912 Used recreationally in 197...

Psychodelics & Hallucinogenics Part 2 MDMA (Ecstasy) MDMA (Ecstasy) 3,4-Methylenedioxymethamphetamine (MDMA) is a mixed stimulant-psychedelic drug! Schedule 1 drug Street names: Ecstasy, Molly, XTC, E, X, Beans, disco biscuit, and Adams. Discovered in 1912 Used recreationally in 1970s Gained Schedule 1 classification in 1985 Used for psychotherapeutic purposes (approved in 2017 by FDA for research into use for PTSD)  MDMA Pharmacokinet ics Route of administration Orally administered in form of tablets, pills, capsules Capsules = Molly Pills/ tablets = ecstasy Absorption & distribution Rapidly absorbed, drug onset 20-60 min post ingestion Peak concentrations ~2 hours after administration, drug effects typically lasting 4-6 hours Readily passes through the BBB MDMA pharmacokinetics Metabolism Metabolized in the liver by CYP450 enzymes Converted into active metabolite: methylenedioxyamphetamine (MDA) Psychedelic! MDMA interacts with several drugs SSRIs enhance effects of MDMA Enzyme inhibitors Excretion Excreted in urine, mostly unchanged Half-life: 9 hours Detectable in urine ~2-4 days  Effects of MDMA MDMA can have psychostimulant effects. Sleep disturbances, suppressed appetite, increased body temp, heart rate/ blood pressure, & respiration, etc. Users experience both psychostimulant AND hallucinogenic effects. These effects are considered reinforcing. Enhanced empathy (primarily in women)  MDMA Pharmacodynamics Primarily effects NE & 5- HT systems Low doses: 1. inhibit packaging of 5-HT into vesicles & 2. reverses monoamine transporters (SERT, NET, DAT) High doses: increase mesolimbic dopamine release  Neurotoxici ty of MDMA Chronic MDMA associated with loss of serotonin neurons in nonhuman primates. These effects were observed up to 7 years out, but mixed human research suggests that the damage done might not be permanent. Repeated use leads to memory and attention dysfunction, which may be partially permanent Other risks: Psychological: paranoia, flashbacks, HPPD. Physiological: hyperthermia (heat stroke) leading to excessive water consumption & water poisoning Organ failure, seizure, stroke, heart attacks  Rebound is common following acute use and results in feelings of depression and lethargy. MDMA Rebound Takes days to synthesize & replenish serotonin/ dopamine stores Users report feeling depressed/ lethargic MDMA Tolerance, dependence, withdrawal Tolerance to subjective effects can develop with MDMA use Pharmacodynamic tolerance Reduced 5-HT, Tryptophan hydroxylase, and SERT following repeated MDMA use Dependence evidence is mixed. MDMA lacks well-characterized withdrawal experience, but rebound effects mimic withdrawal-like symptoms Long-term users may show compulsive use despite negative consequences Heavy use associated with changes in mesolimbic dopamine system, but to lesser extent than cocaine or amphetamines Dissociative anesthetics PCP & Ketamine Dissociative anesthetics Phencyclidine (PCP) and ketamine are dissociative anesthetics Class of drug that causes people to feel separated/ detached from their body or physical environment Dissociatives can cause hallucinations, changes in thoughts, emotions, & consciousness  PCP PCP was developed in the 1950s as an anesthetic but had unusual properties and adverse side effects. Schedule II drug but no longer used or produced for medical purposes in the US! Became a street drug in the 1960s Street names: angel dust, hog, Wack, rocket fuel, ozone, Shermans, Lovelies, Waters  Routes of administration: Injection, snorting, inhalation Orally ingested PCP has poor bioavailability (