By Katharine Santiago
With psychedelics becoming a popular topic of research in the past year or so, it feels fitting to answer some important questions about how they work and what risks may be associated. One of the most common hallucinogens, LSD, is currently a Schedule I drug in the United States, meaning that there is no medical use and it may have a high risk for abuse. This has created a misconception in the public eye that psychedelics are extremely dangerous drugs. However, recent studies suggest that this may be inaccurate, as the recent use of hallucinogens in psychiatric care is a break-through, and may be one of the safer treatment methods that have been assessed.
Because psychedelic drugs have just recently made a return to the public eye after almost six decades, I see a great importance in clearing up any misconceptions that have evolved in that time. Here we focus more specifically on the non-addictive properties of classic hallucinogens, or drugs such as magic mushrooms (the main psychoactive components include psilocybin and psilocin), DMT, DPT, LSD, mescaline, and peyote. All are said to have similar effects because of their shared property as serotonin agonists or partial agonists. This means that these hallucinogens bind to serotonin receptors in the brain, acting on them much like serotonin (an important mood regulator) would.
A study done at Northeastern University in 2017 looked at what may make classic hallucinogens less addictive than other substances. This study specifically compared peyote, psilocybin mushrooms, and LSD to cocaine, a stimulant, or a substance that excites bodily functioning. All classic hallucinogens act on three specific serotonin receptors, 5-HT2A, 5-HT2B, and 5-HT2C, while cocaine effects dopamine (which is important for reward and reinforcement) levels in the brain. The properties of hallucinogens that make them 5-HT 2C agonists have been hypothesized to be the same properties that make these substances non-addictive. This receptor specifically modulates neurons in the nucleus accumbens reward pathway. This reward pathway is the same one that is responsible for positively reinforcing behaviors, thus making them more likely to recur. The research further stated that the activation of this receptor appears to enhance inhibitory activity in the reward pathway, while more addictive drugs such as cocaine have the opposite effect. When a person does a drug that makes them feel good, it reinforces the use of that drug and makes the behavior harder to eliminate (Canal & Murnane 2017).
Classic hallucinogens have the potential to produce strong positive experiences that have been described by many users as life-changing, which is a strong enough positive reinforcer to potentially make these substances addictive. What makes a drug reinforcing and addictive has to do with the increased firing of dopamine neurons in the nucleus accumbens. The projections of serotonin neurons often make direct contact with dopamine neurons, allowing serotonin to control the dopamine systems in the pathway, ultimately causing these neurons to be suppressed. So, the release of serotonin can reduce addictive behaviors by suppressing dopamine transmission.
The 5-HT 2 receptors all activate the same cell signaling pathway, with 2A receptors facilitating dopamine transmission and 2C receptors suppressing it. The activation of the 5-HT 2C receptors is hypothesized to be the mechanism that gives these hallucinogens non-addictive properties because there is no chance for dopamine to be transmitted and the reward pathway to be activated. So even though hallucinogens can create that strong positive feeling in the user, dependency is not established, and an addiction to the substance doesn’t occur. (Canal and Murnane, 2017).
Not only do most of these substances have a very low risk for dependence, but studies have also been done highlighting their use as an effective treatment for addiction to several substances. For example, psilocybin was tested as a treatment for nicotine addiction, and within six months, 80% of the study’s participants were smoke-free. Ayahuasca, which contains dimethyltryptamine (DMT), has been used often by Indigenous groups around the Amazon as well as some religious groups in the U.S.. This drug is activated by monoamine oxidase inhibitors (MAOIs), which facilitate the clearance of serotonin in the brain and are often deficient in depressed patients.
An assessment of mental health on regular users found that they often score lower on the Addiction Severity Index (ASI) for alcohol use compared to those that do not use regularly. The ASI is intended to provide an overview of problems in substance-abusing individuals, and is commonly used in treatment planning and outcome evaluation for those suffering from substance abuse (McLellan, 1980). LSD was one of the first hallucinogens studied for treatment of addiction back in the 1970s. Male inpatient alcoholics were either given a treatment dose of LSD or a smaller amount of LSD mixed with ephedrine and amphetamine (both stimulant drugs) as a control.A meta-analysis from six different randomized trials found that 59% of patients in the treatment group and 38% of control group participants showed significant improvement in their symptoms at the first follow-up, after just one dose of LSD.
While these results did not lead to any significant conclusions, it was enough to reignite interest in this type of research. This study also looked at psilocin, which has similar effects as psilocybin, but has a greater potency in proportion to its size, and has not been used yet to treat any specific addiction, but may be further explored in the future. 5-HT2A receptors play a role, but so may subjective experience, and the lasting psychological changes produced by the use of hallucinogens. People who take psychedelics report having transcendent experiences, which may be responsible for changes in behavior that last far after the drug has worn off. These long-term changes can include changes in certain personality traits, such as an increase in emotional openness as well as an increase in overall life satisfaction. (Bogenschutz et al., 2016)
There is a lot of potential for the use of hallucinogens in the field of medicine. This class of drugs is diverse and unique, but also misunderstood. However, if scientists currently studying these substances can draw significant conclusions that support their use in patient care, I hope that this can change the public’s mind and the government’s opinion as well. The research presented here plays an important role in this, as addiction is an issue that has been plaguing this country for some time, and if there are treatments out there for disorders such as Major Depressive Disorder (depression), Post-Traumatic Stress Disorder (PTSD), and social anxiety that do not create dependence in the user, then a change in the legal status of classic hallucinogens would be a huge step in the right direction in both medical and psychiatric settings. Results from this type of research have been positive so far, and we have seen an improvement of symptoms in participants of these experiments. When it comes to severe forms of psychiatric disorders especially, effective treatments have been scarce until now. Hopefully future research will follow suit, and others will catch on to this potentially ground-breaking revelation in medicine.
Canal, C. E. & Murnane, K. S. (2017). The serotonin 5-HT receptor and the non-addictive nature of classic hallucinogens. Journal of Psychopharmacology, 31(1), 127-143. doi:http://dx.doi.org/10.1177/0269881116677104
Bogenschutz, M. P. & Johnson, M. W. (2016). Classic hallucinogens iIn the treatment of addiction. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64(1), 250-258.. doi.org/10.1016/j.pnpbp.2015.03.002
McLellan, A.T., Luborsky, L., O’Brien, C.P., & Woody, G.E. (1980). An improved diagnostic instrument for substance abuse patients: The Addiction Severity Index. Journal of Nervous & Mental Diseases, 168, 26-33.
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