Hallucinogen
Hallucinogens are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes.[1][2] Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants.[2]
For the 2015 album, see Hallucinogen (EP). For the electronic musician, see Hallucinogen (musician).
Leo Hollister gave five criteria for classifying a drug as hallucinogenic.[5][6] This definition is broad enough to include a wide range of drugs and has since been shown to encompass a number of categories of drugs with different pharmacological mechanisms and behavioral effects.[6] Richard Glennon has thus given an additional two criteria that narrow the category down to classical hallucinogens.[6] Hollister's criteria for hallucinogens were as follows:[5][6]
Glennon's additional criteria for classical hallucinogens are that the drugs in question must also:[6]
Legal status and attitudes[edit]
In the United States, classical hallucinogens (psychedelics) are in the most strictly prohibited class of drugs, known as Schedule 1 drugs.[8] This classification was created for drugs that meet the three following characteristics: 1) they have no currently accepted medical use, 2) there is a lack of safety for their use under medical supervision, and 3) they have a high potential for abuse.[8] However, pharmacologist David E. Nichols argues that hallucinogens were placed in this class for political rather than scientific reasons.[8] In 2006, Albert Hofmann, the chemist who discovered LSD, said he believed LSD could be valuable when used in a medical rather than recreational context, and said it should be regulated in the same way as morphine rather than more strictly.[58]
The Netherlands previously allowed psilocybin mushrooms to be sold, but in October 2007 the Dutch government moved to ban their sale following several widely publicized incidents involving tourists.[59] In November 2020, Oregon became the first U.S. state to both decriminalize psilocybin and legalize it for therapeutic use, after Ballot Measure 109 passed.[60]
Effects[edit]
Relationship between long-term use and mental illness[edit]
No clear connection has been made between psychedelic drugs and organic brain damage. However, hallucinogen persisting perception disorder (HPPD) is a diagnosed condition wherein certain visual effects of drugs persist for a long time, sometimes permanently,[61] although the underlying cause and pathology remains unclear.[62]
A large epidemiological study in the U.S. found that other than personality disorders and other substance use disorders, lifetime hallucinogen use was not associated with other mental disorders, and that risk of developing a hallucinogen use disorder was very low.[63]
A 2019 systematic review and meta-analysis by Murrie et al. found that the transition rate from a diagnosis of hallucinogen-induced psychosis to that of schizophrenia was 26% (CI 14%-43%), which was lower than cannabis-induced psychosis (34%) but higher than amphetamine (22%), opioid (12%), alcohol (10%) and sedative (9%) induced psychoses. Transition rates were not affected by sex, country of the study, hospital or community location, urban or rural setting, diagnostic methods, or duration of follow-up. In comparison, the transition rate for brief, atypical and not otherwise specified psychosis was found to be 36%.[64]
Effects on the brain[edit]
Different classes of hallucinogens have different pharmacological mechanisms of action.[2][65] Psychedelics are 5-HT2A receptor agonists (serotonin 2A receptor agonists).[66][65]
LSD, mescaline, psilocybin, and PCP are drugs that cause hallucinations, which can alter a person's perception of reality. LSD, mescaline, and psilocybin cause their effects by initially disrupting the interaction of nerve cells and the neurotransmitter serotonin.[67] It is distributed throughout the brain and spinal cord, where the serotonin system is involved with controlling of the behavioral, perceptual, and regulatory systems. This also includes mood, hunger, body temperature, sexual behavior, muscle control, and sensory perception. Certain hallucinogens, such as PCP, act through a glutamate receptor in the brain which is important for perception of pain, responses to the environment, and learning and memory.
Thus far, there have been no properly controlled research studies on the specific effects of these drugs on the human brain, but smaller studies have shown some of the documented effects associated with the use of hallucinogens.[67]
Psychotomimetic paradigm[edit]
While early researchers believed certain hallucinogens mimicked the effects of schizophrenia, it has since been discovered that some hallucinogens resemble endogenous psychoses better than others. PCP and ketamine are known to better resemble endogenous psychoses because they reproduce both positive and negative symptoms of psychoses, while psilocybin and related hallucinogens typically produce effects resembling only the positive symptoms of schizophrenia.[68] While the serotonergic psychedelics (LSD, psilocybin, mescaline, etc.) do produce subjective effects distinct from NMDA antagonist dissociatives (PCP, ketamine, dextrorphan), there is obvious overlap in the mental processes that these drugs affect and research has discovered that there is overlap in the mechanisms by which both types of psychedelics mimic psychotic symptoms.[69][70][71] One double-blind study examining the differences between DMT and ketamine hypothesized that classically psychedelic drugs most resemble paranoid schizophrenia while dissociative drugs best mimicked catatonic subtypes or otherwise undifferentiated schizophrenia.[72] The researchers stated that their findings supported the view that "a heterogeneous disorder like schizophrenia is unlikely to be modeled accurately by a single pharmacological agent."[72]