Psychoactive Drugs

Psychoactive Drugs #

Nora Volkow interview May 25, 2023

Nora D. Volkow, MD, is Director of the National Institute on Drug Abuse (NIDA) at the National Institutes of Health

From 39:45

Tim Ferriss: there’s so many incidental or accidental ways to ingest, for example, fentanyl. And I know of many direct stories, where people have gone to a bachelor party, they try a little bit of some drug, that ends up being cut with fentanyl. I know of two people specifically. One just dropped dead on the floor. One fell into a coma from what would’ve been considered low doses of illicit drugs. But they happened to be cut with fentanyl, which is horrifying. And in fact, my friend who died was not himself an addict. He was collateral damage. One of my other friends I grew up with, there are a lot of drug issues where I grew up, was a heroin addict. He had developed just an incredible tolerance to fentanyl, and he gave it to my other friend to help with his hangover. And my other friend had never used any opiates, and he fell asleep and just never woke up. So the sheer ease with which the fentanyl, as you mentioned, sort of permeates different corners and neighborhoods of society, which does not discriminate in terms of — or I shouldn’t say it doesn’t discriminate, but it has infiltrated every socioeconomic class. It’s really pervasive and really terrifying. What is your perspective on the War on Drugs and perhaps any other approaches that you think may be more effective?

Dr. Nora Volkow: Yeah. And I’ll answer it, but I guess actually the story that you just told of your friend that how he’d be taking fentanyl unbeknowing what it was, it just killed him. And this is what we are observing a lot. And I think it’s important to educate people that this is a seriously dangerous drugs. And unfortunately, I think that we have cried wolf so many, many times that we’ve lost credibility. But if there was a way that we could convey that in very objective, we don’t need to exaggerate in any way. I mean fentanyl, two milligrams will kill you. And the counterfeit pills contain five milligrams, some of them two doses to kill you. So it is very, very tragic. But coming back to your question in terms of the War on Drugs, I think that basically what it did was it created a mechanism that could perpetuate structural racism. It is very tragic to see how its enforcement led to the incarceration of young black Americans. And again, that punitive system where someone could be stopped, and this will happen if you are black and on the notion that you had drugs with you and thrown in jail or prison because you had drugs on you is such an unfair system. And it didn’t work in any way because it did not reduce the amount of drugs that people were taking or the negative consequences of drugs to our society. So it did not work. And I think, and too, I mean one of the aspects that it did show is if you do throw a person that’s taking drugs in jail, if you criminalize that person that’s using drugs, for example, when we did horribly with crack cocaine. So if you were smoking crack cocaine, it was like, I don’t recall exactly, but it was at least 10 times greater than if you were just snorting cocaine. Snorting cocaine or injecting cocaine hydrochloride was much more favored by white people. Whereas crack was favored by black people. So cocaine hydrochloride, white, crack cocaine, black. Why do you see such a difference? It’s the same cocaine, basically. Cocaine is cocaine, and yet one could note a much higher penalty than the other. That’s an example of the consequences. But what science has shown is that when you do throw people into jail or prisons that have a problem with substance use disorders, then when they leave, they are at much greater risk of, first of all, relapsing immediately into the drug taking and escalating their drug taking. So you are exacerbating the nature of the problem by putting them in jail and prison. So it doesn’t work no matter what you do. And that’s why the whole notion of criminalizing the person that takes drugs is basically very negative vis-a-vis the outcomes of the person and also in no way it benefits society, it is actually very costly by itself. When an issue becomes politicized, then it becomes much harder to change and shift. And we’ve seen, I think, that we’ve seen over the past, I would say, certainly, five or eight years, an openness to recognizing that the War on Drugs did not work and that criminalizing drug users is basically negative and it’s promoting structural racism.

Show me research on drug harms in the UK

Drug harms

Nutt, D. J., King, L. A., & Phillips, L. D. (2010). Drug harms in the UK: a multicriteria decision analysis. The Lancet, 376(9752), 1558-1565.

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My experience #

Psychedelics are substances that reveal and amplify your inner experience.1

Sacred mandala
Credit: Midjourney "sacred mandala"

I have personal experience with

I am a member of

Psychedelics are not for everybody.

Amplification #

The subjective sense of psychedelic amplification is the reflection of a corresponding impairment of working memory.3 However, working memory is not monolithic. Different psychedelics impair different aspects of working memory. Salvinorin A impairs cognitive working memory much more than emotional working memory. Serotonergic psychedelics impair emotional working memory much more than cognitive working memory.

Predicting Your Reaction to Psychedelics #

Your reaction to a psychedelic strongly depends on the willingness of your Parts to get quiet.4 See my discussion of effortless meditation to learn more about Parts and how to help them relax. There are at least three possible outcomes:

  • Parts are overactive and not willing to get quiet. A psychedelic will tend to make Parts more loud and extreme. This is going to be a difficult trip and corresponds to the monkey mind of an inexperienced meditator 🐒, magnified to Godzilla size 🦍.5
  • Parts are active but willing to get quiet. In this situation, the client gains more access to Self energy and may do Parts work spontaneously. There is the opportunity to make rapid strides toward therapeutic goals.6
  • Parts are fairly quiet. The Self shines with unusual brilliance 🌞 because the psychedelic does the bouncer Part’s job, facilitating an experience of Self that is profoundly effortless. Similar to effortless meditation, there is ample capacity for blending with a target. This is readily seen in reports of music perception under the influence of psychedelics. For example, “Volunteers reported far greater absorption in music, as well as greater perceived beauty and significance of music.”7

Suppose you are curious to try a psychedelic but are not sure whether your Parts will get quiet.

Which psychedelic poses the least risk to the naive user?

Serotonin #


Some of the most popular psychoactive substances operate by modulating the serotonin system. Serotonin is important because it is, in part, responsible for the regulation of serenity.8 Serotonin is also known as 5-hydroxytryptamine, or abbreviated, 5-HT. There are at least 14 different serotonin receptors that allow cells to respond in various ways to the presence of serotonin. The two most prevalent brain receptors are known as 1A and 2A (also called 5-HT1A and 5-HT2A). The figure below shows the function of the two main serotonin receptors.9


Credit: Carhart-Harris & Nutt, 2017, Figure 3

I suggest that psychedelics that target the 5-HT1A receptor pose the least risk to the naive user. The subjective experience is a gentle spotlight on the feeling of soothing comfort. Using this soothing comfort as a target helps tangled Parts relax. Until recently, MDMA and 5-MeO-DMT were the popular psychedelics that seemed to modulate 5-HT1A activity. 5-MeO-DMT directly modulates the 5-HT1A receptor, but MDMA influences it indirectly. MDMA seems to influence the 5-HT1A receptor by its ability to release serotonin (biology is complicated10). In any case, both MDMA and 5-MeO-DMT have disadvantages compared to psilomethoxin. The disadvantage of 5-MeO-DMT is its rapid onset and come down, which can be disorienting. In contrast, psilomethoxin has a user-friendly gradual onset and come down. However, the main advantage of psilomethoxin over these other substances is its legal status. Psilomethoxin is currently unregulated and easy to obtain.

Once there is familiarity with altered states and some confidence is gained in effortless meditation then I suggest the next psychedelic to try is dimethyltryptamine (DMT), a potent 5-HT2A agonist, combined with a monoamine oxidase inhibitor, a combination colloquially known as Daime or Ayahuasca. Pure vaporized DMT has an extremely rapid onset and come down. The monoamine oxidase inhibitor stretches out the journey to about four hours, with a gradual onset and come down. Subjectively, in contrast to psilomethoxin, DMT does not spotlight any particular emotion but facilitates affective unblending in a more pure or indifferent way, demanding more cooperation from Parts to guide the experience.

Unaided, effortless meditation is precarious in the sense that we can not entertain targets that prompt much Part involvement. This is where DMT can pick up the slack. DMT can facilitate Self energy in situations where Parts must exert some effort. For example, Santo Daime is a psychedelic church that has won legal protection in the USA, parts of Canada, and Brazil. In Santo Daime ceremonies, everybody present drinks Daime tea, lead musicians included. Moreover, everybody is expected to sing 🎶 and dance. It seems unlikely to me that new members would often enjoy much Self energy without the help of the psychedelic sacrament. The Daime helps the congregation remain mostly in Self while exerting considerable effort to pronounce Portuguese and precisely synchronize movements to the rhythm 🥁 of the music. The combination of ample Self energy and creative involvement in the ceremony can make for an extraordinarily beautiful experience.

Notes #

  1. Nichols, D. E., Nichols, C. D., & Hendricks, P. S. (2022). Proposed Consensus Statement on Defining Psychedelic Drugs. Psychedelic Medicine. ↩︎

  2. I am a bit embarrassed to be affiliated with Catholicism given its sordid history. In general, I admire the best of all of the world’s religions. ↩︎

  3. Healy, C. J. (2021). The acute effects of classic psychedelics on memory in humans. Psychopharmacology, 238, 639-653. ↩︎

  4. Aday, J. S., Davis, A. K., Mitzkovitz, C. M., Bloesch, E. K., & Davoli, C. C. (2021). Predicting reactions to psychedelic drugs: A systematic review of states and traits related to acute drug effects. ACS Pharmacology & Translational Science, 4(2), 424-435. ↩︎

  5. The potential adverse events are similar to what you might get with a meditation session gone wrong, but worse. ↩︎


  7. Barrett, F. S., Preller, K. H., & Kaelen, M. (2018). Psychedelics and music: Neuroscience and therapeutic implications. International Review of Psychiatry, 30(4), 350-362. ↩︎

  8. Olivier, B., & Mos, J. (1990). Serenics, serotonin and aggression. Progress in clinical and biological research, 361, 203-230. ↩︎

  9. Carhart-Harris, R. L., & Nutt, D. J. (2017). Serotonin and brain function: a tale of two receptors. Journal of Psychopharmacology (Oxford, England), 31(9), 1091-1120. ↩︎

  10. Ray, T. S. (2010). Psychedelics and the human receptorome. PloS One, 5(2), e9019. ↩︎