Hallucinogen ClassificationKey Points About Hallucinogens (1)Why Research Hallucinogens?How Research Hallucinogens?Two-way Active Avoidance: Shuttlebox Experimental ParadigmHallucinogen Effects on Shuttlebox AvoidanceImportant Unanswered Questions Re’ Hallucinogenic Drug ResearchHallucinogens - Hallucinogens: natural and synthetic (synthesized) substances that significantly alter one's state of consciousness- May cause people to see (or think they see) random colors, patterns, events, and objects that do not exist. - May cause people to have a different perception of time and space, hold imaginary conversations, believe they hear music and experience smells, tastes, and other sensations that are not real. - May have profound emotional effects: the user may feel in touch with others around them or with their inner self, feel closer to God or the universe or just feel ecstatic, enhancing enjoyment of musicand dancing and being with other people.Hallucinogen Classification- Most often classified as hallucinogens, solely because of their capacity to produce hallucinations. - Because of their varied effects, have also been classified as "psychedelic," ("mind-expanding" drugs) and “psychotomimetic,” (“mimicking psychosis”)- Four major classes (Cross tolerance w/in each class confirms this grouping and common biological sites of action w/in each class):Monoamine-related Substances- LSD- mescaline - MDMA (ecstasy)structurally related to monoamine neurotransmittersCannabinoids - Marijuana (THC) chemical derivatives of plant cannabis sativaAnticholinergics - Scopoloamine- atropineantagonists of Acetylcholine (ACH) receptors; hallucinatory experiences at high dosesDissociative Anesthetics- Phencyclidine (PCP) - ketamineprofound anesthesia, awake but appear disconnected from environment, distortions of body image, feelings of depersonalization, sense of timelessness and beingin ‘outer space’Key Points About Hallucinogens (1)- Differ from other abused drugs, like opiates and amphetamines, in important ways: Hallucinogens are not physically addictive (habit-forming); however, people can become psychologically dependent upon them. Hallucinogens are not self administered—their effects are not mediated by the reward (pleasure centers) of the brain, but rather their reinforcing value is derived from its ability to alter perception and consciousness.- The real danger of hallucinogens is not their toxicity (poison level), but their unpredictability. People have had such varied reactions to these substances, especially to LSD, so that it is virtually impossible to predict the effect a hallucinogen will have on any given individual. Their context-dependent effects are influenced by the person's mood, surroundings, personality, and expectationswhen taking the drug.- Have been revered in many societies for their use in religious rites or as medicinal agents. Their usein modern Western societies has been much more controversial. - On the one hand, they are considered to be dangerous drugs: the Federal Bureau of Narcotics and Dangerous Drugs has placed them in Schedule I, the most restrictive class. The general public has had a positive, yet controversial, attitude towards them, in part because of their association with the antiwar and countercultural movement of the 1960s. They were used by relatively few people in the United States until the social upheaval of the 1960s.- By the mid-sixties, seemingly overnight, LSD and marijuana use was common across the country, especially among the young. Many books were written to explain or vilify this phenomenon, many others to justify the use of these drugs (e.g., Aldous Huxley's The Doors of Perception), where Huxley writes of his experimentation with mescaline in Mexico; LSD, which was virtually unknown to American society in the early sixties and still legal until 1966, gained widespread recognition as a result of the very public exploits of so-called acid gurus, Timothy Leary and Ken Kesey.Why Research Hallucinogens?- Because they produce profound changes in perception and affect, hallucinogenic drugs might provide some insight into these basic psychological processes and may be a special window to the mind-body problem.- Some consider them to be of particular interest from a mental health perspective since they are psychotomimetic - that is, their effects mimic certain aspects of the major psychoses and they may be a research model of naturally occurring psychoses. - Because their impressive effects are often produced by minute quantities (microgram amounts in the case of LSD), hallucinogenic drugs are of particular interest to those who study the brain; their potency implies that the drugs act with specificity at particular sites within the brain. How Research Hallucinogens?- Neurobiological Methods – e.g., electrophysiology, biochemistry- Behavioral Methods – e.g., conditioning paradigmsTwo-way Active Avoidance: Shuttlebox Experimental ParadigmLight = CS (top right circle)Light  shockShuttling stops shock (escape response) or prevents shock (avoidance response)Hallucinogen Effects on Shuttlebox Avoidance - LSD and mescaline facilitate acquisition of shuttlebox avoidance (excitatory effect)- LSD and mescaline disrupt performance of shuttlebox avoidance (inhibitory effect)- There is no tolerance to the excitatory effect—stress related—”bad trips”- There is rapid tolerance to the inhibitory effect—non-stress related—”good trips”Bridger et al, 1973; Stoff et al 1974Important Unanswered Questions Re’ Hallucinogenic Drug Research Research is limited by the ability to get good animal models in view of the unique subjective effects ofhallucinogens in humans- Why are hallucinogenic drug experiences so variable and unpredictable?- What is the precise mechanism of action of hallucinogens and the anatomical substrate?- What underlies the mental experiences of hallucinogens