Drug Dangerousness: A History of Psychedelics PDF

Drug Dangerousness - Opium is a chemical compound extracted from the seed pods of opium poppy plants - Opioids are substances that contain opium or its psychoactive constituents or chemically similar drugs - Synthetic opioids are synthetically produced drugs chemically similar to...

Drug Dangerousness - Opium is a chemical compound extracted from the seed pods of opium poppy plants - Opioids are substances that contain opium or its psychoactive constituents or chemically similar drugs - Synthetic opioids are synthetically produced drugs chemically similar to naturally occurring opioids. - For instance, fentanyl is a synthetic opioid used as an analgesic and anesthetic - - Heroin has been cut with increasingly larger amounts of the more powerful fentanyl until medical examiners were seeing overdose cases in the United States in which only fentanyl had been used. - In mid-2016, carfentanil, the most potent commercially available opioid, began to show up on the illicit drug market and in death investigations in the United States. - No drug has been specified but opioids contribute to 25 percent of death certificates for overdose deaths - David Nutt made an evaluation of drug dangerousness which was based on acute reactions to drugs, long-term dependence, and its social and healthcare impacts - The first thing to notice about the relative dangerousness of drugs is that psychedelic drugs are not regarded as more dangerous than some other legal and illegal drugs Modern History of Psychedelics - The British-born psychiatrist Humphry Osmond who coined the neologism “psychedelic” in 1956 to mean mind-manifesting or soul revealing had been the director of the Weyburn Mental Hospital, about 115 kilometers south of the university - Osmond’s director of research was a Canadian psychiatrist, Abram Hoffer - Mental hospital in the middle of the Canadian prairies would become the world's most important job of research into psychedelics The invention of LSD - In 1938, Albert Hofmann was looking for new medicine at the Sandoz company in Basel, Switzerland, when he produced a new chemical, the 25th in a series of lysergic acid compounds that he designated as “LSD-25” - He thought that LSD could possess properties other than those established in the first investigations and so he produced some once again - On April 16, 1943, during the last stage of the synthesis, he was interrupted in his work by feelings of restlessness and slight dizziness, forcing him to go home - At home he laid down and closed his eyes, he found that his imagination was so stimulated that for 2 hours he “perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with the intense, kaleidoscopic play of colors” - Hoffman thought that some of the LSD had been absorbed through his fingertips during the crystallization process  - Three days after his first experience, Hofmann took what he assumed to be a conservative dose of 250 micrograms of LSD, unaware of the potency of the drug that he had created - He went home again on his bike, that day is now known as Bicycle Day by lsd aficionados - The large does force him to lie down. Everything began to spin, and familiar objects and pieces of furniture assumed grotesque, threatening forms. - He believed to be outside his body and wondered if he was dying - After some time it began to feel like the first experience all over again, suns became changing, vivid images, each with its consistent form and color - The following morning he felt refreshed and found sensory experiences to be extraordinarily pleasurable - He believed this drug could be useful in psychiatry, by 1960 more than 500 papers about lsd had been published - A guy named John Lilly obtained some LSD-25 from the Sandoz company and injected himself with 100 micrograms before climbing into an isolation tank; he was terrified, having received warnings of doing LSD without supervision. - His awareness of his body and brain in the tank disappeared, all that was left was a small point of consciousness in a vast domain - He felt that light was being formed into atoms and atoms into light directed by a vast consciousness - The first article concerning LSD in 1947 was called Phantasticum, particularly in the field of drug laws and medical research - The world illusion genic has been proposed as an alternative to hallucinogens - Psychedelics are psychotropic in the sense of being mind-altering - Psycholytic means mind dissolving - These drugs have also been called psychotomimetic meaning mimicking or inducing psychosis - Psychedelic drugs that appear to provide extrasensory empowerment have been called telepathines The Psychedelic Sixties - In the 1960s psychedelic drugs received a substantial impetus during the 1960s from Timothy Leary - When he took psychedelic drugs for the first time he had a deepest religious experience, convincing him that he had awakened from a long ontological sleep a process he characterized as turning on - Turning in refers to harnessing one's internal revelations to the external world - Dropping out referred to the pursuit of an authentic spiritual quest - Leary believed that people's lives consisted of playing games of which they were unconscious but from which the psychedelics could liberate them - By the late 1960s, psychedelic drugs had spawned a counterculture with characteristic lifestyles, leaders, status distinctions, and internal rivalries. - Which could be found in enclaves in cities around the world  - Those who used LSD were charged by the authorities with being “sick and dangerous” to which drug advocates replied that it was they, the established powers, who were sick and dangerous - Medical personnel and lawmakers were accused of approving enslaving drugs such as alcohol and nicotine and prohibiting the liberating psychedelics - LSD had become the sacrament that provided anyone who wanted them with visionary experiences that had previously been the property of solitary mystics and esoteric collectives James Fadiman who had been introduced to psychedelics by Richar Alpert was one of a group of researchers giving psychedelics to artists, engineers, architects, and scientists in the san Francisco Bay Area to see whether it could enhance creativity - Participants reported greeted mental fluidity and increased ability to visualize and recontextualize problems - Some engineers even went as far as crediting LSD for contributing to the birth of the computer revolution in Silicon Valley where “interest in psychedelics as a tool for creativity and innovation” - Osmond traveled to Leary saying what he was doing was dangerous, Osmond tried renaming the psychedelics a second time by introducing the neologism psychedelic as a way of trying to distance legitimate research from the drug's more frivolous use, but that did not work. - LSD continued to be available to physicians till 1963, its availability was restricted in 1966 - In 1968 possession became illegal throughout the United States - Then in 1970 the Comprehensive Drug Abuse Prevention and Control Act was put in place, and many psychedelic drugs became Schedule I controlled drugs, a designation that indicated a lack of safety even in medically supervised use, high abuse potential, and no current accepted medical use - A study in a 1990 questionnaire survey of Tibetan Buddhist practitioners, found that 77 percent of 64 respondents reported previous experiences with major Psychedelics, whereas 32 percent claimed that major psychedelics had contributed at least somewhat to attracting them to Tibetan Buddhism Renaissance - A quarter-century after being banned some government-sanctioned research with psychedelics quietly resumed in the early 1990s - In the 1990s however, the strategy was to consider these drugs as any other drugs to be investigated, not for their phenomenological but for their physiological and neurological effects, with possible eventual uses - For example in the treatment of “severe substance abuse” and “pain and depression” associated with terminal illnesses - In 2006 three events occurred that shifted the attitudes toward the potential benefits of psychedelics  - The first was the celebration of Albert Hofmann’s 100th birthday, with an accompanying symposium, which drew 200 journalists and over 1000 participants from various backgrounds - The second was a decision by the U.S Supreme Court to allow the religious sect Uniao do Vegetal to import the psychedelic brew ayahuasca into the United States for its ceremonies - The third was the publication of an academic paper reporting the results of an experiment at John Hopkins Uni in Baltimore, in which volunteers were given the psychedelic mushroom psilocybin and so a decade later there are more clinical trials in psychedelics happening today, both for basic effects and therapeutic purposes, than at any time on history Varieties of Psychedelics - LSD is one of the most potent drugs known with doses as small as 10 micrograms producing some mild euphoria - Psychedelic effects begin at around 50 to 100 micrograms and increase up to about 400 or 500 micrograms - The typical dose is 50 to 150 with effects beginning within 45 to 60 minutes after ingestion - Effects can be increased heart rate, blood pressure, and body temperature, dilated pupils, and mild dizziness - The psychoactive effects of drugs can differ depending on the set and setting - Set refers to the expectations that a person has at the time of taking the drug - Setting refers to the physical, social, and cultural environment in which a drug is taken - There can be dramatic mood swings from happiness to sadness and back again - There is the possibility of shape-shifting and the question of whether the Tamang shaman Bhirendra experienced himself in a manner that was similar to that of the anthropologist under the influence of LSD Psilocybin - McKenna ate a mushroom known as the Stropharia cubensis - He ate the whole thing and continued his walk, things began to stand out with a new presence and significance - Stropharia Cubensis is one of about 90 mushroom species that contain psilocybin or psilocin which were identified and named by Hofmann in 1958 after examining Psilocybin, the more stable of the two compounds, gets converted to psilocin when ingested - 15 milligrams or more of psilocybin results in a trip that generally lasts from two to five hours - The physiological effects of psilocybin are like LSD but gentler and the psychological effects are similar to those of LSD except that they tend to be more visual, less intense, and less dysphoric Mescaline - The peyote cactus, containing more than 30 psychoactive substances, including mescaline, is one of several cacti with psychedelic effects that have been used by native people from northern Mexico and the southwestern United States from at least as early as 100 BCE - One way of ingesting peyote is to cut and dry the tops of cactus to for buttons that can be eaten - The buttons have a bitter taste and can cause vomiting headaches and nausea - An effective dose of mescaline is about 200 milligrams or about three to five buttons, with effects lasting from 8-12 hours - The drug is said to produce more intense physiological arousal and to result in a more sensual, perceptual, and stable trip than LSD - Huston Smith, upon taking mescaline at one of Leary’s parties, was struck by the apparent fact that the drug “ACTED AS A PSYCHOLOGICAL PRISM” revealing multiple layers of the mind among which he could move at will by shifting his attention - Furthermore seeing the structure of these layers of reality had the force of the sun against which everyday experience reveals only flickering shadow in the dim cavern DMT - Dimethyltryptamine (DMT) has been found throughout the living natural world, including the human body and brain, and has also been synthesized - When 50 milligrams or more of DMT are smoked or injected, effects similar to those of LSD except for greeting intensity begin almost immediately and after about a half-hour - Study down by Rick Strassman at the University of New Mexico - He injected participants with various doses of DMT - One of the striking results was the finding that with a sufficiently high dose, an individual would report the experience of having been propelled into a world that appears to exist independently of the individual mind - Another participant said “You return not to where you left off but to where things have gone since you left - Furthermore contact with aliens being experimented on in highly technological settings, implantation of devices, and transmission of information have been found with DMT intoxication - Also been found that the pineal gland, a ting gland in the middle of the brain that produces melatonin could be the source of DMT surge - The answer is no, nor is there any production of the amount of DMT that would be required to create otherworldly experiences Ayahuasca - Found in upper Amazon in South America, Indigenous people, including many shamans drink a psychedelic cocktail for which they have over 70 manes, including ayahuasca, the one that we are using  - Ayahuasca is made by pounding and cooking in water the woody Banisteriopsis vines, such as Banisteriopsis caapi usually adding any of 90 additional different plants to “lengthen and heighten the intoxication” - Banisteriopsis itself contains several psychoactive ingredients such as the beta-carbolines, including “harmine, harmaline, and tetrahydroharmine” - About 200 milligrams of harmine or harmaline are needed for a 4-8-hour trip - The inclusion of Psychotria viridis adds DMT to ayahuasca - Normally DMT is broken down in the stomach by monoamine oxidase - The addition of DMT to ayahuasca is said to make for “better and brighter visions” Ayahuasca is known as a purgative in part because it induces vomiting and severe diarrhea - There can be a sense of flying images of colored lights geometric patterns and animals such as jaguars, birds, and reptiles as well as visions of spirit helpers, demons, deities, and distant events - At one time the psychoactive ingredients of Banisteriopsis were named telepathines, presumably to reflect the alleged extrasensory empowerment that they provided - Ayahuasca tourism began in the 1990s, as travel to consume ayahuasca has come to be called, now involves tens of thousands of travelers - Ayahuasca has been touted as a panacea that can cure pretty much anything with some apparent successes - The message is that native psychedelic enthusiasm needs to be tempered with knowledge about the reality of ayahuasca tourism Neuropharmacology of Psychedelics - In the context of drug use, the term tolerance refers to the need for increased amounts of a substance to achieve a desired effect or “a markedly diminished effect with continued use of the same amount of the substance - Tolerance for LSD develops “within two or three days” and then disappears just as quickly - The pattern of tolerance is similar for psilocybin, mescaline, and DMT - There is a cross-tolerance between many of these drugs meaning that intoxication with one of them will inhibit the effectiveness of a second one if it is taken shortly after the first - Investigators reasoned that psychedelic effects result from the mediation of serotonergic neural pathways in the brain - They tend to increase activity in serotonergic pathways by stimulating the 5-HT2 subtype of serotonergic receptors - However, a psychedelic can both excite and inhibit by attaching to different receptors on the same neuron - Paradoxically, the activity of the MDN is attenuated, which could account for transformations of self-identity, including death and rebirth experiences - Taken drugs together, these neurological modifications could shift a person out of their usual ways of perceiving and conceptualizing themself and the world into others, which may be more meaningful or less meaningful than the previous ones Long-term effects of Psychedelics - There can be an increase in hypnagogic imagery, and dreams may take on the vividness intensity, and perceptual peculiarities of drug trips Perceptual Effects - Perhaps the most common adverse effect is the occurrence of flashbacks, the transitory recurrence of emotions and perceptions originally experienced while under the influence of a psychedelic drug that can last for just seconds or hours and can include any of the features of the drug experience itself - Flashbacks can sometimes be triggered by intoxication with drugs such as marijuana and selective serotonin reuptake inhibitors - There is a psychopharmacological resemblance between psychedelics and SSRIs with not only reports of SSRIs triggering flashbacks but an apparent heightening of SSRI activity by psychedelics - The perceptual aspects of flashbacks have been subsumed in a broad category of post-psychedelic perceptual disturbances called hallucinogen persisting perception disorder - These long-term alterations of perception can last from seconds to years and can include, among other distortions, intensification of color, changes in size, images of geometric forms, images in the peripheral visual fields, afterimages, and stationary images of moving objects - One way to think about this is to note that the brain appears to function in a manner that maintains synaptic homeostasis so that flooding receptor sites with chemical agents that can activate them leads to a compensatory attenuated response - IN 2 studies done, repeated administration of LSD to rats was found to decrease the availability of the 5-HT2 receptor subtype in the other study chronic administration of LSD for seven days was found to result in alterations in the behavior of rats that were detectable in more than thirty days after the drug treatment Psychotic Effects - Given that changes to serotonin receptor binding have been noted in those with schizophrenia, that some medication used in the treatment of schizophrenia blocks 5-HT2 receptors, and that some psychedelics can elicit schizophrenia-like symptoms in humans, it has been hypothesized that excessive 5-HT2 receptor activation may be a critical factor in psychotic in schizophrenia, at least in some cases - If this is true, then psychedelics could precipitate schizophrenia - Can psychedelics cause some form of psychosis resembling schizophrenia that persists after the termination of a drug trip, certainly there have been those who have experienced mood swings, visual hallucinations, mania, grandiosity, and religiosity, following the use of LSD. - Incidence figures for psychosis following use of psychedelics have ranged from 0,008 to 4.6 percent - It was found that 37-49 percent of those hospitalized for LSD psychosis had received previous psychiatric treatment  - In a direct comparison of people with schizophrenia with and without previous drug use and a control group of people without schizophrenia, it was found that those using drugs had better psychological adjustment before the onset of schizophrenia than those not using drugs but worse psychological adjustment than the non schizophrenic individuals - The problem with the previous drug use study was the conflation of the effects of psychedelics with those of other drugs, given that hallucinogens were not the only drugs previously used by the participants - For those with schizophrenia who had used drugs, multiple drug use was common, making it difficult to implicate any single drug as a causative agent for chronic psychosis, not only because of the confounding effects of the other drugs but also because of the psychotomimetic effect of different drugs of abuse can be addictive - Differences have been found between acute psychoses that developed 2 to 7 days after using LSD and psychoses in which no drugs had been used, suggesting that some people may be vulnerable to psychosis induced by psychedelics Psychedelic Treatment of Alcoholism - Hoffer and Osmond noted the similarities between delirium tremens, the hallucinations reported by people in the throes of alcoholism, and psychotomimetic experiences under the influence of LSD - Hoffer and Osmond speculated, giving alcoholics a high dose LSD session to mimic delirium tremens before they sink to that stage. And they did, with apparently good results, although they came to reconceptualize the LSD experiences as instances of mystical transcendence rather than psychosis - Arnold Ludwig and his colleagues randomly assigned 176 alcoholic hospital inpatients into four groups of 44 each - All of the participants receive milieu therapy, a form of humane institutionalized care - One group only received the milieu therapy, those in a second group received, in addition, a single LSD session, those in a third group received psychotherapy as well as LSD, psychotherapy, and hypnosis - The researcher's rationale for the last of these combinations was that the use of hypnosis would allow the LSD sessions to be more structured and hence greet therapeutic benefit - Participants in this group would receive a high dose of LSD and then be hypnotized while the LSD took effect - Once the drug effects began, participants would be left in discussions of their major problems and then give posthypnotic suggestions to continue working on their problems and to make a greater effort to accept responsibility and lead a more productive life - Then hypnotized participants in LSD sessions were left alone in a room with paper and a pencil in case they desired to write about their experiences - In Ludwig's study, even though the dramatic accounts were written by participants in the letter part of their sessions “were all that could have been hoped for”, there was no evidence that any of the LSD sessions made a difference in therapeutic outcome at follow up intervals of up to 1 year  - In conclusion, there were either no differences in outcomes with the use of LSD or the differences disappeared by the time of 6-month follow-ups - Given the serious social burden posed by alcoholism and the fact individuals seeking treatment have had 3.6 previous treatment attempts, illustrative of the failure rate of conventional forms of treatment, psychedelic treatment is being reexamined to see if there are ways of harnessing it as an effective treatment for alcohol use disorders Psychedelics in Palliative Care - Stanislav Grof has done extensive research concerning the administration of psychedelic drugs to those who are dying of cancer - The purpose of the psychedelic therapy was “not treatment of cancer, but relief from emotional and physical pain and change of the attitude toward death through deep mystical experiences induced by psychedelics - The analgesic effects of psychedelics have sometimes persisted for weeks after their acute effects have worn off - Psychedelics have also changed people's attitudes toward death - Common among those who have had transcendent experiences - The ontological awakening that sometimes accompanies psychedelic experiences appears to reconcile some people to their impending death Transcendental Effects of Psychedelics - The Good Friday experiment - In which students were given psilocybin before participating in a Good Friday service on April 20, 1962 The Good Friday Experiment - Walter Pahnke, a doctoral student in religion and society at Harvard - To determine the extent to which experiences described by mystics were similar to those induced by psychedelics - 20 participants were prepared for the experiment in a manner that was meant to maximize positive expectation, trust, confidence, and reduction of fear - Divided into 5 groups of four, in addition, two leaders familiar with the effects of psilocybin, assigned to each group - Two of the student participants in each group received 30 milligrams of psilocybin and one leader 15, while the other two students and the other leader each received 200 of nicotinic acid - The point was to have been a double-blind study so that those in the experimental and control groups could not identify who was in which group - Eighty minutes after swallowing their capsules, the participants in the Good Friday experiment moved into a small prayer chapel - After 2 hour service, the participants remained in the chapel and nearby rooms until the effects of the drug had worn off  - Data was collected immediately after, within days, and at 6 months, in additio,n they did a long-term follow-up 24-27 years later with nine of the participants from the control group and seven from the experimental group - The study revealed statistically significant differences in scores between the experimental and control groups on all of the characteristics of mystical experiences except sacredness - One who received psilocybin said he lapsed into a period of complete lostness of self and another said that the more he let go the greater sense of oneness he received - Alleged ineffability associated with mystical experiences is found in the comment by a participant who said that he cannot describe the sense of the divine - With the right set and setting the use of psychedelic drugs can lead to experiences with characteristics that are similar to mystical experiences Varieties of Psychedelic Experiences - Mike Young was a participant in the Good Friday experiment who got psilocybin - His experience began gently, with the intensification of colors, etching of geometric figures around objects, and the presence of afterimages trailing people with moved - He had difficulty keeping track of what was happening inside and what was happening outside his head - Young felt that he was at the center of the circle immobilized - He has said that then he died, and, in dying, realized the freedom of becoming who he could be - Years later, he understood this vision to be about his struggle to make a career choice - Young has said his experiences that “religious ideas that had been interesting intellectually before now were connected to something much deeper than belief and theory - Psychedelic experiences, no matter the preparation are not necessarily uniformly pleasant - Out of 7 interviewed who took the psilocybin only two had a please experience that was completely positive without significant psychic struggles - Huston Smith, one of the group leaders had an unpleasant experience - He recalled that the participant had gone to the front of the chapel, where he had given an incoherent homily, blessed the congregation with the sign of the cross - Then left the chapel, found an open door, left the building, and took off down the street The Johns Hopkins University Experiment - Follow-up study, 40 years after which 36 participants received either 30 milligrams of psilocybin or 40 milligrams of methylphenidate hydrochloride - They arrived on 2 occasions not knowing if they would receive the psychedelic or the active placebo - Eleven percent of participants rated the psychedelic experience as the single most meaningful experience of their lives whereas 58 rated it as being among the five most personally meaningful experiences of their lives - 64 percent felt that the psilocybin session had increased their sense of well-being or life satisfaction - Eleven of the participants indicated that they had experienced extreme fear at some point during the session - Four reported that a significant portion of their session was characterized by anxiety/dysphoria and an additional four reported that the entire session had been like that - Three said that they never wanted to have an experience like that again - Overall 61 had a complete mystical experience compared with 30 to 40 participants in the Good Friday experiment