Shrinks In Sneakers

Tag: psychedelic

  • Setback for MDMA Therapy: FDA’s Rejection and Key Concerns Explained

    Setback for MDMA Therapy: FDA’s Rejection and Key Concerns Explained

    The FDA’s decision to reject MDMA (methylenedioxymethamphetamine) for medical use typically stems from various concerns related to safety, efficacy, and potential for abuse.

    Background

    MDMA is primarily known as a recreational drug, often associated with rave and party scenes. However, it has been studied for its potential therapeutic benefits, particularly in the treatment of post-traumatic stress disorder (PTSD) and other mental health conditions.

    Safety Concerns

    1. Neurotoxicity: Research has shown that MDMA can be neurotoxic, causing damage to serotonin-producing neurons in the brain. This can lead to long-term cognitive deficits, including memory problems and mood disorders.
    2. Cardiovascular Risks: MDMA increases heart rate and blood pressure, which can pose significant risks to individuals with underlying heart conditions. The stimulant effect can lead to hyperthermia (overheating) and dehydration.
    3. Acute Toxicity: Overdose can lead to severe hyperthermia, serotonin syndrome, and even death. The narrow therapeutic window between a therapeutic dose and a toxic dose is a significant concern.

    Efficacy Concerns

    1. Clinical Trial Results: While there have been promising results in some clinical trials, the FDA requires extensive, well-controlled studies to confirm a drug’s efficacy. If trials do not meet these rigorous standards, the FDA may not approve the drug.
    2. Long-term Benefits: The long-term efficacy of MDMA therapy is still uncertain. While short-term benefits have been observed, there is a need for more data on the sustainability of these effects.

    Potential for Abuse and Addiction

    1. Recreational Use: MDMA is widely used recreationally, which increases the potential for misuse and addiction. The FDA must consider the risk of the drug being diverted for non-medical use.
    2. Dependence: There is evidence that regular use of MDMA can lead to psychological dependence, and managing this risk is crucial in the context of medical approval.

    Regulatory and Ethical Considerations

    1. Ethical Concerns: The use of a psychoactive substance in a therapeutic setting raises ethical questions, particularly regarding informed consent and the management of potential adverse effects.
    2. Regulatory Framework: The FDA has stringent requirements for approving new medications, including ensuring that benefits outweigh risks. For a drug like MDMA, where the risks are significant, the bar for approval is high.

    Conclusion

    The FDA panel recently rejected the use of MDMA-assisted psychotherapy for treating PTSD, marking a significant setback for advocates of this treatment approach. The advisory committee, in a vote of 9-2, concluded that the current evidence does not support the effectiveness of MDMA in treating PTSD. Additionally, they voted 10-1 against the benefits of MDMA therapy outweighing its risks​. 

    Several key concerns led to this decision. Firstly, issues were raised about the integrity and validity of the clinical trials conducted by Lykos Therapeutics, including potential biases, functional unblinding, and allegations of misconduct. The panel also highlighted gaps in the data, particularly regarding the potential for abuse and adverse cardiovascular events associated with MDMA​​.

    Despite the panel’s recommendation, the FDA is not obligated to follow their advice, though it often does. The outcome has disappointed many proponents of MDMA-assisted therapy, who argue that the treatment could provide much-needed relief for PTSD patients who have not benefited from existing therapies​. 

  • How to Change Your Mind: The Current State of Psychiatry and Psychedelics

    How to Change Your Mind: The Current State of Psychiatry and Psychedelics

    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. 

    I’m 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. 

    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 wasn’t 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.

    What’s the story are we ready to prescribe everyone psilocybin and MDMA as a form of mental health treatment? 

    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). I’m not sure how correct this theory is but it’s 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 1940’s 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 1970’s 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. 

    Classes of Hallucinogens 

    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.

    Classic Hallucinogens 

    -Tryptamines: psilocybin, LSD, and DMT 

    -Phenethylamines: Mescaline 

    Non-Classic Hallucinogens 

    -3,4-methylenedioxymethamphetamine (MDMA)

    -Dissociative Anesthetics: Ketamine, PCP, Dextromethorphan 

    Therapeutic Targets for Psychedelic Use

    Disorders Under Investigation: 

    -Depression 

    -Anxiety

    -PTSD

    -OCD

    -Cancer related stress and psychological issues 

    -Addiction 

    -Smoking cessation 

    -Sexual dysfunction 

    -headaches 

    -inflammatory disorders 

    Maybe the best studied area is in end of life and palliative care settings. 

    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 psychedelics 

    Neurobiology

    People often make comments like we don’t know how much serotonin is enough, then conclude that medications do work or the therapies we are using are invalid. That’s 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. 

    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 “trip” is required to produce a therapeutic effect. 

    Side Effects of Psychedelic Use 

    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 

    -visual disturbances

    -disorganized thinking

    -paranoia

    -mood changes 

    Hallucinogen Persisting Perception Disorder (HPPD) 

    -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.