ADHD (Attention-Deficit/Hyperactivity Disorder) affects millions of adults worldwide, with stimulants like methylphenidate and amphetamine being the most effective treatments. But could psychedelics like LSD offer an alternative? A new randomized clinical trial aimed to find out.
Intervention: Low-dose LSD (20 Όg) or placebo twice weekly for 6 weeks (12 doses total)
Primary Outcome: Change in ADHD symptoms using the Adult ADHD Investigator Symptom Rating Scale (AISRS)
đĄ Key Findings:
Both groups showed significant improvement in ADHD symptoms:
LSD group:Â â7.1 points (95% CI, â10.1 to â4.0)
Placebo group:Â â8.9 points (95% CI, â12.0 to â5.8)
â LSD was safe and well tolerated
â No significant difference between LSD and placebo in symptom reduction
đ§ What This Means: While low-dose LSD was safe, it didn’t outperform placebo in treating ADHD symptoms. This challenges anecdotal claims about psychedelics for ADHD and reinforces the need for rigorous placebo-controlled trials in psychedelic research.
đ Future research may explore higher doses or alternative mechanismsâbut for now, stimulants remain the gold standard for ADHD treatment.
Should LSD be considered a treatment for generalized anxiety disorder (GAD)? The results from MindMed’s Phase 2b study suggest it just might be. While this is only one study, and the FDA’s cautious stance on psychedelic-based treatments like MDMA raises questions about future approval, the findings are worth exploring. So, letâs dive in.
GAD is a fascinating and somewhat controversial diagnosis. Notably, the study excluded participants with major depressive disorder, a condition frequently comorbid with GAD, which raises interesting questions about the choice to isolate GAD. Some in the psychiatric field even challenge the validity of GAD as a distinct psychiatric disease, arguing it reflects broader distress rather than a discrete disorder.
Psychedelics like LSD are surging to the forefront of psychiatric research, largely because the field is starved for innovation. Decades of research and sophisticated drug development have yielded limited breakthroughs in understanding or treating psychiatric conditions. Meanwhile, society often clings to the hope that complex human behavior and mental health challenges can be reduced to something as simple as a pill you take every 12 weeks. The appeal of psychedelics lies in their potential to disrupt this paradigmâbut can they deliver?
Key Findings:
Dose-Dependent Response:
Patients receiving a higher dose (200 ”g) of MM-120 showed rapid and sustained improvements in anxiety symptoms.
The reduction in anxiety symptoms was statistically significant compared to the placebo group.
Speed of Onset:
Improvements were observed as early as two weeks post-dosing, suggesting a rapid therapeutic effect.
Duration of Effect:
The anxiety-reducing effects lasted up to 12 weeks following a single administration, indicating long-lasting benefits.
Safety Profile:
The treatment was generally well-tolerated, with mild to moderate adverse effects such as headache, nausea, and transient emotional changes. There were no reports of severe adverse events related to the study drug.
Mechanistic Insights:
MM-120 appears to modulate serotonin 5-HT2A receptors, leading to enhanced neuroplasticity and emotional processing, which may underlie the observed clinical improvements.
Iâm always interested in the study population and if the researchers selected a group of patients with prior psychedelic use. Here is what I found
Participant Screening and Inclusion:
Prior Psychedelic Use:
Some participants may have had previous experiences with psychedelics (e.g., LSD, psilocybin, MDMA), as long as such use did not interfere with the integrity of the study (e.g., recent or habitual use, which might influence tolerance or expectations).
Individuals with significant past psychedelic use might be excluded to minimize potential biases in response to the trial drug.
Psychedelic-NaĂŻve Participants:
The trial likely included a substantial proportion of participants who were psychedelic-naïve, meaning they had never used substances like LSD or psilocybin before.
This approach helps ensure that the observed therapeutic effects can be attributed to MM-120 rather than prior familiarity or psychological preparation for psychedelic experiences.
Why Prior Use Matters:
Expectation Bias:
Participants with past psychedelic experiences may anticipate certain effects, influencing subjective outcomes like anxiety reduction.
Safety and Tolerability:
Previous exposure to psychedelics might affect how participants tolerate or respond to the treatment.
Generalizability:
Including both psychedelic-naĂŻve and experienced individuals helps make the findings applicable to a broader population.
Implications:
This study suggests that psychedelic-assisted therapy, especially with compounds like MM-120, has significant potential as a novel treatment for GAD, offering rapid and durable relief after just one dose. These findings pave the way for further research and larger-scale trials.
Pink cocaine, also known as tucibi or 2C-B, is a synthetic hallucinogen from the phenethylamine family, first synthesized in the 1970s. Despite the “cocaine” in its street name, it is chemically unrelated to cocaine. It usually comes in powder form but can also be found in tablets. It’s popular in party scenes for its euphoric and stimulant effects, which are often compared to a combination of MDMA and LSD.
At higher doses, it can cause anxiety, paranoia, and dissociation.
Effects can last from 4-8 hours depending on the dose and mode of administration (oral, nasal).
Health Risks:
Cardiovascular issues, including hypertension and tachycardia.
Risk of psychosis and mood disorders, especially with repeated use.
Hyperthermia and dehydration, especially in party environments.
Possible neurotoxic effects, though research is limited.
Addiction and Dependence:
While physical dependence is not common, psychological dependence can develop due to its euphoric effects.
Patients may use it in cycles with other substances (e.g., MDMA, alcohol), leading to polysubstance abuse.
Withdrawal:
No specific withdrawal syndrome has been documented, but patients may experience depression, anxiety, and cravings after discontinuation.
Management may require addressing underlying mental health issues or substance use patterns.
Treatment:
Cognitive-behavioral therapy (CBT) or motivational interviewing may help address compulsive use.
Monitor for concurrent use of other drugs, especially stimulants or hallucinogens, as polysubstance abuse is common.
Referral to harm-reduction programs may be beneficial for patients unwilling to quit completely.
Legal Status:
It is illegal in most countries, classified as a Schedule I drug in the U.S. However, enforcement is inconsistent, and it continues to be accessible in underground markets.
For addiction psychiatrists, it’s crucial to recognize tucibi use, especially in patients with party-drug histories. Understanding the psychological effects and potential for dependence will aid in developing a comprehensive treatment plan. Monitoring for concurrent substance use and educating patients on the risks is key.
There is no hotter topic in the world of psychiatry than the reemergence of psychedelics as therapeutic tools for the treatment of mental illness. When esketamine was approved by the FDA in March of 2019 it opened the doors for medications like MDMA, psilocybin, and mescaline as possible therapeutic agents.
Iâm excited about these new options for therapy but I also want to make sure the science backs up the personal experiences of individuals who use these medicines in uncontrolled settings.Â
Introduction:
The psychedelic era was a time of social, musical, and artistic change influenced by the use of psychedelic drugs that occurred between the mid-1960s and mid-1970s. Although this era lasted for some time it largely fell out of favor for legal reasons and wasnât a topic in modern psychiatric training until just recently. It seems like overnight there are New York times articles, Netflix documentaries, and evening news coverage about psychedelics.
Whatâs the story are we ready to prescribe everyone psilocybin and MDMA as a form of mental health treatment?Â
History of Hallucinogens in Medicine
For over 5 millennia humans have been attempting to alter their state of consciousness. Some have argued it goes even further back to primate ancestors who consumed large quantities of ripe fermented fruit to alter their state of consciousness (drunken monkey hypothesis). Iâm not sure how correct this theory is but itâs safe to say psychedelics have been around for a long time.
In 1943 Albert Hofmann a chemist by training, invented LSD by accident. He started the research in 1938 and announced that he sampled the chemical in 1943. Not only did he synthesize it, but he was getting high on his own supply. In 1957 this same chemist isolated psilocybin from the hallucinogenic mushrooms.
In the 1940âs LSD was marketed as a drug to assist psychotherapy, the so-called drug assisted psychotherapy which is making a comeback today. Unfortunately, of the 1000 studies published looking at psychedelics as a model for psychosis and as therapy were small and uncontrolled.
In the 1970âs most of these medicines were placed into schedule I status making it exceedingly difficult to study the medicines further for therapeutic effects in a controlled setting. A Randomized controlled trial is considered by many to be the highest standard of scientific evidence.Â
Classes of HallucinogensÂ
For years people thought of psychedelics as LSD or psilocybin, the term now includes other medicines. The term psychedelic is derived from two Greek words meaning mind manifesting. Essentially psychedelic and hallucinogen are being used interchangeably these days but do have separate meanings.
Maybe the best studied area is in end of life and palliative care settings.Â
Mechanism of Action
-The primary mechanism of action is 5-HT2A receptor stimulation
-5-HT2A is the most abundant serotonin receptor in the central nervous system and cortex of the brain.
-Stimulating the 5-HT2A receptors will increase the release of glutamate in the cortex
-Stimulation of 5-HT2A receptors in the visual cortex can lead to visual hallucinations. Stimulation in the ventral tegmental area can produce a situation like that of schizophrenia with delusions and hallucinations.
-Most atypical antipsychotics bind to and block 5-HT2A receptors and would mitigate the effects of psychedelicsÂ
Neurobiology
People often make comments like we donât know how much serotonin is enough, then conclude that medications do work or the therapies we are using are invalid. Thatâs because they are thinking about mental illness and these medications too simply. Most psychiatrists do not believe in or talk about the chemical imbalance theory of treating mental illness. We think about mental illness and problems with neural circuits, nodes, and networks. What medications including the psychedelics achieve is an alteration in the connectivity of these networks and the ability to form new connections.
We have a default mode network which is famously active when a person is not focused on the outside world and the brain is just daydreaming. What psychedelics do is decrease brain connectivity in this default mode network followed by the establishment of new connections.
Hypothetically this rewiring of the brain allows for the replacement of faulty connections resulting in mental illness and the formation of new healthy connections through psychotherapy provided during treatment. This may be why the antidepressant effects last far beyond other interventions with less frequent dosing.
There are identifiable changes in network connectivity that coincide with subjective improvement.Â
The Mystical Experience: Is Tripping Required for a Therapeutic Effect
-There is a mystical experience questionnaire that has been validated and used in these studies. It seems that the more profound the mystical experience the better the treatment effect subjectively
-While the spiritual experience many individuals have while taking these medicines is profound and meaningful to the individual, we are not sure that having a âtripâ is required to produce a therapeutic effect.Â
Side Effects of Psychedelic UseÂ
While some may claim there are no adverse effects from plant-based medicine that is not true.
Things like increased blood pressure, berating rate, and body temperature have been reported.
-Loss of appetite, dry mouth, sleep disturbance, uncoordinated movements, panic, paranoia, psychosis, and bizarre behaviors
Long-Term Effects:
Persistent Psychosis: A series of continuing mental problems including
-Recurrences of certain drug experiences such as hallucinations or visual disturbances
-These experiences often happen without warning and may occur within days of last use or even years after taking the drug
-These experiences can be mistaken for neurological disorders such as strokes or brain tumors.
Conclusion
At this time what we can say about the current state of psychedelics in psychiatry is they are under investigation. We do not know yet if they are safe and effective for treatment of mental illness on a mass scale. We have some encouraging evidence but there is an absence of large randomized controlled trials proving efficacy and safety. Psychedelics are not ready for clinical practice and should not be recommended as a treatment for mental illness until the proper studies have been conducted.
