In 2004, a team of pharmacologists from the University of Michigan School of Medicine, led by William Fantegrossi, undertook to testing for psilocybin addiction potential – a hallucinogenic compound derived from certain fungi – on a cohort of rhesus monkeys. The researchers presented a group of primates with a lever that, when pressed, injected them with a dose of the compound. A second group was connected to levers that injected a simple saline solution.
In similar experiments, monkeys are known to repeatedly press the levers that inject drugs heroin, cocaine and even methylenedioxymethamphetamine (MDMA). This is a phenomenon that researchers attribute to the “strengthening effects” of these drugs. But when it comes to psilocybin, the results have been mixed. Some have pressed the lever repeatedly to the point of drunkenness; others have vowed to remove the lever for good after a dose. On average, the monkeys were no more inclined to self-administer psilocybin than the less exciting saline.
Scientists are reopening a line of investigation into the therapeutic applications of psychedelic compounds that was abruptly closed after the drugs were first banned in the 1960s. The rhesus monkey study is one of the many pieces of evidence something researchers have suspected for decades: Unlike other widely used recreational drugs, some psychedelics are not reliably addictive. The growing body of research was seen as a “psychedelic rebirth. ”
A different path
While we tend to think of addiction in terms of human behavior, it has neurological roots. In the brain, addiction manifests itself in what researchers call the “reward path”. When a person is stimulated by a reward – a chocolate cake, their favorite song, good sex – the brain responds by increasing the available concentration of dopamine, a neurotransmitter. This response, in moderation, is experienced as a pleasure.
Most recreational drugs, including caffeine, alcohol, nicotine, marijuana, opiates, and cocaine, artificially increase the available concentration of dopamine in your brain. In other words, they create a feeling of pleasure independent of natural stimuli. Psychedelics, on the other hand, work in an entirely different way.
The term “Classic psychedelics” is used by researchers to refer to a family of chemically similar drugs called tryptamines which include psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT) and mescaline (the psychoactive component of peyote). These compounds are distinct from compounds like ketamine and phencyclidine (PCP), which are sometimes called psychedelics but have an entirely different mechanism of action.
Although classic psychedelics have little affinity for dopamine receptors, they mimic another neurotransmitter: serotonin. In particular, these compounds bind to a certain serotonin receptor found throughout the brain and which has been shown to be involved in mood regulation, facial emotion recognition and memory.
Unlike most drugs, however, a person’s psychological response to tryptamines is highly unpredictable. A person could take psilocybin and have a deep, joyful experience. Another might take the same dose and endure anxiety or horror. “Classic psychedelics are unreliable,” says Matthew Johnson, psychedelics researcher at Johns Hopkins Medicine. “Even if you have an optimal environment, for the same person sometimes it is happiness and sometimes it is terrifying. It’s not an easy drug escape if that’s your goal.
Users of almost all drugs experience a decrease in effects after regular use. The same dosage of opiates could knock out a novice user while simply staving off the cravings of an addict. But for psychedelics, tolerances can develop much faster.
In a 2016 chapter on psychedelics in Pharmacological advice, pharmacologist David Nichols writes that “the daily administration of LSD essentially leads to a complete loss of sensitivity to the effects of the drug on day 4”. Even if a user attempted to get around this by spinning through different psychedelic compounds, the effects would be greatly diminished if not eliminated. Studies have shown that tolerance to LSD also results in tolerance to psilocybin and mescaline.
Together, these three factors – the lack of effect on dopamine levels, the unreliability of the psychedelic experience, and the rapid onset of tolerance – are believed to contribute to the low potential for addiction in conventional psychedelics.
According to Administration of Addiction and Mental Health Services, the proportion of patients reporting hallucinogens as the main substance of abuse did not exceed 0.1% from 2005 to 2015. In comparison, the proportion of patients reporting alcohol as the main substance of abuse is never fell below 33%.
If you browse the growing body of research on psychedelics, you won’t find many articles dealing with the addictive potential of tryptamines themselves. Instead, you will come across a number who are studying the effectiveness of these compounds in treating substance abuse disorders. In particular, LSD can be a alcoholism treatment and psilocybin, along with therapy, can help people nicotine addiction.
Read more: Psychedelics could be the future of psychotherapy
In October, the National Institutes of Health awarded a team led by Johnson the first federal grant for research on psychedelic treatments for over half a century. The nearly $ 4 million grant will allow researchers to conduct the first-ever, double-blind, randomized clinical trial of psilocybin as a treatment for nicotine addiction.
“I didn’t know if it would be this year or five years from now,” Johnson says, “But, with the data continuing to come out that shows these really promising effects, it was almost unthinkable that the NIH would choose not to for the finance.