Despite its classification as a Schedule 1 substance, recent research suggests that LSD has low abuse potential and does not typically lead to dependence.
Overview: LSD, a psychedelic compound known as "acid," was extensively researched for its therapeutic potential in the 1950s and 60s but fell out of favor due to unreliable outcomes and eventual prohibition. Recent studies have renewed interest in LSD for mental health treatment, and it is found to have a low potential for abuse and dependence compared to addictive substances like opioids or alcohol. LSD primarily acts on the serotonin system in the brain, unlike addictive substances that affect dopamine release. Tolerance to LSD develops quickly, making habitual use unlikely. LSD also has a low potential for overdose.
The psychedelic compound lysergic acid diethylamide (LSD), commonly known as "acid", was a prominent tool in psychedelic research during the "golden age" of the 50s and 60s. It was used in the treatment of chronic pain and mental health conditions such as alcohol addiction, with over 40,000 patients receiving LSD-assisted therapy and numerous scientific papers published on its healing potential.
However, primitive research designs of that time led to unreliable outcomes, and the therapeutic value of LSD remained uncertain. LSD research and therapy went dormant after its eventual prohibition in 1968 classification as a Schedule 1 substance where it is deemed as having no accepted medical use and high potential for abuse.
Despite being classified as having no accepted medical use and a high potential for abuse, LSD has a low potential for abuse, is not physically addictive and typically does not lead to dependence like opioids or alcohol, and recent studies have demonstrated its therapeutic potential.
As the renewed interest in psychedelic compounds for mental health treatment grows, people are questioning how LSD compares to current treatments in terms of efficacy and side effects.
When considering the addictive potential of psychedelic compounds such as LSD, it is important to understand their impact on the human brain. Unlike addictive substances like alcohol, nicotine, cocaine, amphetamines, and opioids, which directly or indirectly stimulate dopaminergic neurons and elevate dopamine levels in the brain to produce transient feelings of pleasure, psychedelic compounds do not act in the same way.
The effects of chronic consumption of addictive substances often lead to persistent release of dopamine, resulting in euphoria and excitement, and implanting drug cues into the amygdala, a brain region involved in emotional processes and motivation. This can trigger obsessive craving for these habit-forming substances and lead to addiction as users seek to chase a high or numb physical or emotional pain.
During periods of abstinence, the addicted user's brain may be primed to re-engage in drug use when triggered by single use of the drug, environmental cues, craving, withdrawal, or stress, even in the face of negative health or social consequences. Additionally, drug-induced deficits in impulse control and decision-making can further contribute to the compulsive drive to engage in drug use.
However, psychedelics like LSD do not share the same mechanism of action as addictive substances and do not produce the same effects on dopamine release or addictive behaviors.
In contrast, a large population study of 130,000 adults published in the Journal of Psychopharmacology in 2015 concluded that the use of LSD is not associated with mental health problems, including addiction. According to the study's authors, “psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use.”
This is because "classical psychedelics," such as LSD, psilocybin, mescaline, and DMT, primarily interact with the serotonin neurotransmitter system, rather than the dopamine system. Specifically, LSD exerts its psychoactive effects through action at the 5-HT2A serotonin receptor, a mechanism that is not associated with the pleasurable reinforcing effects observed with drugs of abuse. Unlike addictive substances, the use of psychedelics does not typically promote redosing, suggesting a low potential for abuse.
Researchers have concluded that addiction to classic psychedelics, including LSD, is highly unlikely for the majority of people due to the overall lack of activity with dopamine receptors. Since recreational use and research on LSD began in the 1940s, it has not shown any dependence liability. In general, psychedelic compounds do not induce cravings in the same way as other drugs.
Furthermore, the intensity, long duration of action, and unpredictability of the LSD experience, which can be challenging, likely lead recreational users to limit their frequency of use. This information supports the idea that classic psychedelics, including LSD, are not typically associated with addiction or compulsive use.
The development of tolerance is a hallmark of addiction, where users require increasingly higher doses of their drug to feel its full effects. For addictive drugs like cocaine, tolerance builds up slowly over time, making users more prone to addiction and negative effects. In contrast, tolerance to psychedelic drugs like LSD develops quickly, making it difficult to achieve the same psychoactive effects after just a few days of use.
In 2016, pharmacologist and medicinal chemist David Nichols conducted a review on LSD and found that “daily administration of LSD leads essentially to complete loss of sensitivity to the effects of the drug by day 4.” As an expert in the pharmacology of psychedelics, Nichols believes that there is no motivation to continue using LSD habitually if it fails to produce psychoactive effects.
The exact reason for the rapid development of LSD tolerance is still unknown, but repeated administration has been shown to downregulate 5-HT2A receptors in the brain, which means there are fewer binding sites for LSD to produce its characteristic effects. Additionally, repeated LSD use has been shown to reduce the binding affinity of glutamate - the brain's most abundant neurotransmitter - and the responsiveness of glutamate receptors in the cortex of LSD-tolerant rats. This may further explain the fast development of LSD tolerance.
Increased tolerance to addictive drugs can lead to life-threatening overdoses, but LSD is unique in that it has a low potential for overdose. Approximately 31 million people in the US have used LSD, with no documented deaths due to recreational doses. While a few LSD-related fatalities have occurred, they are typically a result of engaging in dangerous activities while under the influence.
Cross-tolerance, which occurs among all classical psychedelics, means that taking psilocybin today will significantly diminish the effects of other classic psychedelics, such as LSD or mescaline, tomorrow.
Before prohibition, LSD was considered as a potential treatment for alcohol-use disorder. Alcoholics Anonymous co-founder Bill Wilson became a proponent of LSD-assisted therapy for alcohol addiction after participating in a supervised trip as part of a controlled experiment in 1956. Wilson believed that the spiritual implications of an LSD experience could aid in overcoming addiction. However, this hypothesis was dismissed by his peers, and he left the organization two years later.
Recent research, including a meta-analysis of six randomized controlled clinical trials conducted between 1966 and 1970, has provided support for Wilson's intuition regarding the anti-addictive potential of LSD. The analysis found that a single dose of LSD had a significant beneficial effect on alcohol misuse.
Meanwhile, psilocybin has shown promising results in treating smoking addiction when combined with cognitive behavioral therapy. An open-label pilot study published in 2014 found that 2-3 psilocybin-assisted therapy sessions could result in substantially higher abstinence rates compared to current treatments. After 12 months of psilocybin treatment, 67% of participants remained abstinent from smoking.
As a recognition of their pioneering research, the researchers at Johns Hopkins who conducted this study recently received a $4 million grant funded by the National Institutes of Health. This grant will support a three-year, multi-site, double-blind, randomized controlled trial to further investigate the effects of psilocybin-assisted therapy on smoking addiction.
Many people believe that psychedelics, like alcohol, tobacco, cocaine, and opioids, have the potential for abuse and harm. However, psychedelics, particularly classical psychedelics like LSD, are among the least harmful of all psychoactive substances in terms of physiological safety and addiction potential, especially when used in moderate dosages and controlled environments.
LSD is considered non addictive, and there is potential for LSD-facilitated interventions to be integrated into future addiction treatment approaches, which could be a positive addition for those who have not found success with traditional addiction treatments.
It's important to note that dissociative anesthetics like ketamine and phencyclidine (PCP), as well as entactogens like MDMA, are often referred to as psychedelics, but they are distinct from classical psychedelics and have different mechanisms of action that may promote addiction or compulsive use.
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