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.
It’s obvious to me, but I think the public, including many of our patients, remains unaware of a crucial truth: Psychedelics will not cure your depression, your PTSD, or your difficult life circumstances.
There’s a growing wave of enthusiasm around psychedelics as miracle cures for mental health conditions, but the hard reality is that the evidence just doesn’t back it up—at least not yet. Even if you find yourself on the hopeful side, believing we desperately need alternatives to alleviate people’s suffering, the reported benefits of these substances have not been validated by large, rigorous, randomized controlled trials. The buzz around psychedelics often overshadows the fact that they lack the necessary scientific backing to support their mainstream use in treating complex mental health issues like depression or PTSD.
Let’s not ignore the financial stakes here either: The people promoting these drugs stand to make billions of dollars. There’s a lot of money on the table, and many in the academic community are rallying behind these companies. But we should ask ourselves—are they doing so because of solid science or because of the potential financial windfall?
These drugs have been around for decades, yet one consistent truth I’ve observed in every person I’ve known who’s used them is this: You must use them repeatedly, and they almost always experience a relapse of symptoms over time. There’s no permanent fix here, just a temporary reprieve, if even that.
We can draw parallels with other treatments like ECT (electroconvulsive therapy) and ketamine. Both have shown promise in certain cases, but I’ve yet to see anyone cured by these treatments. We often perform maintenance ECT and maintenance ketamine therapy for this very reason. Just like psychedelics, they might offer temporary relief, but they don’t provide long-term solutions without ongoing interventions.
I understand this may come off as cynical, but I’ve seen too many people fall for the hype, only to be disappointed later. People far more charismatic than me will try to convince you that psychedelics will cure everything that ails you—for a hefty price tag. Don’t buy into it without questioning the science and the motives behind the push.
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
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.
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.
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
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.
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
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.
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
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.
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.
The entactogen MDMA overlaps with the chemical structure of methamphetamine and mescaline and has biological effects similar to epinephrine, dopamine, and serotonin.
It increases the release of monoamines through the reversal of transporter proteins and reuptake inhibition specifically serotonin and norepinephrine. Not only does it block reuptake of serotonin and norepinephrine it enhances the release as well and inhibits VMAT preventing the packaging of monoamines into vesicles making more available for release. It also modulates glucocorticoids through the HPA axis, decreases amygdala and hippocampal activity, increases oxytocin, and increase prefrontal cortex activity.
Medical Use
MDMA started out as a therapeutic agent to enhance blood clotting for surgical procedures and trauma. Turns out it does not work very well for that indication, who would have thought. It’s currently listed as a schedule I substance (defined as having no accepted medical use, high abuse potential, and lack of accepted safety).
It was later discovered to have “empathogenic effects” helping individuals who use the medication to feel more connected to their fellow human beings. After all isn’t that what we are all after? A deep connection to others and people who truly understand us. The original name for the drug was empathy, but that has changed over the years to molly and escstcy. Personally, I like names that describe what a drug does, and empathy or empath is just so much more marketable don’t you think?
Why PTSD is a Big Problem
With several recent wars in both Iraq and Afghanistan, America has a PTSD problem with many combat veterans returning home and requiring treatment. If you ever treated patients with PTSD than you know it’s difficult and the therapy can be intense. Many patients are unable to sit with the discomfort required to reconsolidate these memories. Having worked at the VA for one year I was surprised by the number of vets with non-combat related PTSD. Honestly, they the vast majority of my cases were people who had accidents while working or in training and subsequently developed PTSD.
The idea is we need methods to enhance the efficacy and speed of trauma focused psychotherapies. What better way to do that than with empathy a medication that enhances feelings of connection. The basic idea being the patient would be given MDMA and then undergo psychotherapy and by using the medication it can influence fear extinction and memory reconsolidation. There are many mechanisms at play including effects on dopamine, serotonin, BDNF, cortisol, and oxytocin.
The concept of using a psychedelic drug to enhance the effects of psychotherapy is not a new concept, and was done for years using LSD and other compounds. What is different now, is we are trying to put the scientific rigor behind the studies to prove that it works better than placebo, and to learn more about the mechanism of action.
I want to point out that the main benefit of all these psychedelic medications seems to be enhanced neuroplasticity and the ability to form new connections in critical neurocircuits much easier than would otherwise be possible.
Benefits of MDMA Assisted Psychotherapy
-Increase blood flow to the vmPFC decreasing activation of the amygdala largely responsible for the fear response
-Enhance the production of BDNF which improves the long-term potentiation and memory consolidation
-Elevate the stress hormone cortisol which interacts with glucocorticoid receptors in the hippocampus to improve memory
-Elevates the prosocial neuropeptide oxytocin which decreases activation of the amygdala and enhances connection with the therapist
-Increased levels of dopamine which can destabilize the old memories and help with reconsolidation of new ones
-Increased serotonin levels resulting in prosocial and positive affective states.
The goal of PTSD treatment is to prevent the patient from being held hostage by these memories. We want to destabilize the old memories, modify them, and reconsolidate the new memories. The trauma still occurred, but the patient no longer has the same fear reaction to the traumatic memories.
MDMA-Assisted Therapy proved to be highly effective in individuals with severe PTSD.
-In this study investigators gave patients with PTSD 120-180 mg of MDMA along with a trauma focused psychotherapy. There were significant rates of both response and remission compared to placebo.
-MDMA was well tolerated
-It was granted breakthrough status by the FDA
-This was a big deal in the news and media outlets
-It needs to be replicated to confirm the results
Potential Adverse Effects of MDMA
-Potential for abuse and diversion (probably no take homes)
-Possible hyperthermia or hyponatremia (more common in the recreational use environment than clinical)
-People often engage in prolonged physical activity in hot environments and do not consume enough water this results in dehydration and possible hyperthermia (think large dance party)
-In the opposite case the person overcompensates and overconsumes water diluting their blood and causing hyponatremia. Excess of anything can cause problems and water is no exception.
Blue Monday and Black Tuesday
-Use of MDMA can cause low mood, irritability, and fatigue. It can occur for days after recreational use.
-In the clinical setting, fatigue, anxiety, low mood, headaches, and nausea can occur in the week after treatment
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.
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
-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.
