Organised by the UNODC Research and Trend Analysis Branch with the support of the International Society for the Study of Drug Policy
The side event will explore the current clinical research of psychedelic compounds in treating a range of mental health conditions. Ongoing Phase 2 and 3 trials in the United States and Europe using MDMA, psilocybin, and other psychedelics suggests that emerging therapies might be available to patients by the end of the decade. Presently, several jurisdictions are considering alternative policies aimed at making these compounds more accessible. This event will describe some of the ongoing clinical research in using psychedelics to treat depression, anxiety, post-traumatic stress disorder, and other conditions and what that means for related policy.
Chair: Angela Me, Chief, Research and Trend Analysis Branch, UNODC
So our question was – what are the new research issues that we want to discuss – what’s happening from the medical research on use of psychedelics, but on the perception of what psychedelics might be good or not good for? From our research perspective – what is the implication of the evidence that we have now, for drug policy? The perception is similar to what has happened for cannabis – with psychedelics, it’s faster than the research side. So – where are we in the research?
Gabriella Gobbi, Professor, McGill University
Research sponsored by Canadian Government. Psychedelics have been used for 3000 years. In the western culture, psychedelics more popular in 1938 when Hoffman synthesised LSD. Also, psilocybin was available for research. From this time, until 1970, there was a lot of psychedelic research, when the US scheduled many psychedelics.
Slide – Serotonin Hallucinogens
Tryptamine – Psilocybin and psilocybin (magic mushrooms), DMT (ayahuasca), Lysergamine (LSD) ergot, Phenethylamine (Mescaline) peyote.
MDMA – not a serotonergic – pure synthetic, synthesised in 1912 – empathogenic.
Recent studies:
- LSD plus psychotherapy in anxiety disorders – complex study, started with placebo. You can see a clear reduction in anxiety.
- Psilocybin psychotherapy in AUD – decrease in % of heavy drinking days.
- Psilocybin plus psychotherapy in major depression – only two doses of psilocybin were effective compared to daily medication of Escitalopram.
- MDMA + psychotherapy for PTSD – able to decrease significantly the symptoms of PTSD. First clinical trial
We’re really interested in understanding how psychedelics as medication work. E.g. using low does vs high doses. LSD mechanism of action has some similarities to Prozac, and LSD increases neuroplasticity.
Slide – recent regulations of psychedelics in the world
Matthew Johnson, Johns Hopkins University
Focusing on psilocybin and the effects on mental health. Conflicts disclosed.
Psilocybin in >200 mushroom species. Classic psychedelics – psilocybin, LSD, mescaline, DMT. Ancient uses of psilocybin date back to a cave painting in Algeria 9000 years ago. 1940-70s – promising findings for cancer-related distress and alcoholism, I have focussed a large portion of my work on abuse liability and risks (2008 & 2018). I have researched bad trips. One risk that isn’t there with classic psychedelics – not addictive (but can be abuse). These treatment models don’t require daily dosing. They are mostly based on psychedelic therapy model where a physician available in case of emergency.
So there’s this construct called mystical experience that has roots going back to William James. It sounds a little like it’s referring to the supernatural but it really just refers to the psychological experience that one has. Sort of the mystical experience refers to a number of things but primarily having a sense of unity such as feeling it one with the universe or one with the rest of humanity and unveiling a sense of transcending time and space and some other constructs but when we look at that we do see this relationship between decreased anxiety and depression six, five weeks later, being correlated with the degree of mystical experience as measured in self-report at the conclusion on that session day where people received it.
It’s the nature of the experience, very similar results by our colleagues at New York University published at the same time in some previous research by trying to grow up at UCLA, now moving into depression outside of cancer, some early promising results by the Imperial College Group published in 2016, showing reductions in depression for at least three months. So similar results of randomised trial. So you see these data most another large trial, over 20 patients large reductions in depression, for addiction. I’ll skip past this historical research, but we reach out results with smoking cessation with very high levels. As abstinent six months after our treatment with three sessions of psilocybin, which really looks much larger than existing treatments.
In our pilot study, mystical experiences be related to the outcomes. We’re almost done with a randomized study compared to make a team patch and right now, we’re seeing for over 60 people about a doubling of success for year out, compared to nicotine patch. We’ve gotten a US federal grant to continue that research in the US. Very similar line of research by our colleague, Michael Bolden acutes at NYU. We think there’s something very interesting trans diagnostically connecting these disorders. People seem to be mentally stuck in a self-optimal way of being involved these disorders. And so it seems that the commonality is that we need to figure out the mechanisms or so but these sessions have this profound ability and some people to get them unstuck and to get them out of that sub optimal routine.
Jan Ramaekers, Professor, University of Maastricht
Psychedelics in same chemical club as psilocybin – DMT – long psychedelic experience (depending on the dose you take. Can be complicated in hospital settings. DMT and 5-MeO-DMT. Onset of the experience can be very fast. Entire experience can last 10-20 mins. Both are fast acting, short duration.
Ayahuasca – comes from the Amazon for spiritual and religious purposes. Complicated in terms of its constitution. It is a psychedelic and can be used to alter and improve mental health. Comes from observational studies – it’s mostly used outside of clinics (in Europe, US, everywhere) where you can pay fees to drink Ayahuasca. After the exposure to ayahuasca, we’ve seen reductions in depression (within 24 hours). Not everyone has a response though – some non-responders.
Researchers/small biotech companies have produced a synthetic version of DMT to treat symptoms of depression. D’Souza – published in 2022. Looking at a low dose and a higher dose of DMT. More recently – top line results published from Small Pharma – treating with an active dose of DMT or placebo – 30% of those in active group when into remission, only few in the placebo group. These people then went into an open label study and then 60% went into remission. In D’Souza study, there was some minimal psychotherapy.
Did some fieldwork with 5MEO DMT – participants volunteered to inhale toad venom – here were saw improvement in mental health outcomes. However, these were health volunteers, not patients. Measured magnitude of psychedelic experience – higher the dose, higher the magnitude of psychedelic experience – and then the stronger the decreases in symptoms.
Reckweg et al 2021 slide – shows that it is very short acting, could do multiple doses. We didn’t know the recreational dose, so started very low. Everybody reached the peak experience.
Discussant: Rosalie Liccardo Pacula, Professor, University of Southern California
I’m convinced there is opportunities for different doses for different substances. So when we talk about psychedelics and the policies towards psychedelics, I think it would be better to think about which psychedelic because as we heard from the three presenters, there are some differences in terms of what they do in our bodies in the light and a level the clinical evidence differs when you’re thinking about changing policies, because this is what the debate is about.
When you’re talking about medicine, there’s a typical medical process that requires a certain body of products. The most samples that are shown here have relatively small samples. We think of those as more like clinical trials or getting quotes. What what’s, what’s unique about this is these are studies that are being published in a really good strong scientific journal. This is different than cannabis quite honestly, cannabis while there is still the same level of studies that love the evidence of the science publication wise where it’s published is not as strong a signal about the robustness of the spine. Here, the science since there, it’s getting there and we’re moving to those next stages. If the decision is to make it available medically to change policy, so it’s available medically. That has tremendous gains for for our patients. There is recommended dosing, it’s highly regulated and the product that is delivered has advantages to a product in the case of the psychedelics that in many cases, is a complaint. Relating plants. We have very good agencies and all of our countries, that Department of Agriculture, they’re very good at regulating what the environment is around the plant to make sure the plant thrives.
But those agencies aren’t as good at understanding what’s inside of the plant and what that does to our bodies. That science is usually held in a different regulatory body which is where medicine we have we move a policy forward if we aren’t thinking about the regulatory environment to set up a system that protects the consumer, whether they’re a medical consumer, or a non-profit. That part of what you want to think about in these debates. The other thing that you want to think about is whether it’s appropriate to schedule coming from the Global North. My bias I will be just upfront is to go through a medical route where it is a known product because of the North access to those medications isn’t as difficult as a campaign that needs to be considered when thinking about the international treaties and whether or not to be included in those treaties. It was part of the debate with Canon just a few years ago. It was a plan it was a psychedelic in the US at the schedule two drug war and make available in the for medical purposes already through our standard medical normals. That’s because it’s not scheduled internationally.
We do have lots of nations experimenting. It goes beyond both Canada and a few US states. In fact, in the US, we have a special focus program for MDMA already going so each drug clinically, in terms of policy is being treated strategically because of evidence of scientific body kindness. We go to that international forum and say, what is the best treatment for these drugs we really need to be thinking about access to what looks to be very promising medication and what vehicle through which that can be made available. The rules we’ll get a five internationally will set the rules within each country and how they’re allowed to count and that can have implications for local us. Thank you
Caitlin Hughes, Incoming President of ISSDP
My role is to think about this in terms of legal and regulatory issues that we think about as we think about converting the science into rolling out these policies in different countries. What I wanted to know is that, as our first speaker outlined, that there have been a few different countries that have started to put into practice some different models for accessing substances, whether that’s for describing or different substances. And I think what’s interesting is that already you can see some quite different types of models. So for example, if you have to think about Denver, Colorado, which in May 2019 has decriminalized psilocybin. Here the initiative is very much about reducing prosecution to people who are present, but also enabling people to grow their own psilocybin. So that’s one type of model, then we have Oregon. It’s a different type of model again, because here for Oregon, they legalised psilocybin but they have also rolled out a range of fairly stringent outside medical conditions and systems under which it needs to be used. There’s manufacturing requirements. And there’s requirements for testing purest purity potency, there’s also no requirement that the product will only be able to be purchased, possessed and consumed at licensed facilities using a specially manufactured products and under the supervision of trained facilitators that have returned to Australia where I live. Last month the Australian Therapeutic Goods authority made the decision that from the first of July this year, medicines containing both psilocybin as well as MDMA can be prescribed for a number of conditions. The range of conditions here is more limited. It’s only for treatment resistant depression, and PTSD. In this instance, prescribing will be limited only to psychiatrist and only two psychiatrists who have obtained permission through authorized prescriber scanning and so that they can control the circumstances under which people have assets. So it’s a very medicalized model again. So policies differ on in a number of way because one is about what medical conditions are which access is afforded. Another is how is the drug obtained? Do people grow themselves after they had to obtain from the black market? Do they get it from a new white market? Is it a medical is a synthetic product? There’s also been questions about the context under which one we use. Is it in a very medicalized setting? Is it in open status as we’ve heard in many parts of Latin America, or is it in someone’s own personal use and then you’ve got questions about the level of medical oversight about the sessions. I think there are still further themes that we’ve seen for the presentation today. That for each substance, it’s probably likely to require somewhat of a different model regulatory response. I think more broadly, what we’ve learned throughout looking at medical cannabis, as well as looking at models of decriminalization or legalization of cannabis, is that the design choices really do matter. And so I think it’s probably we’re probably at a sort of tipping point to start to think about different types of models, or access to these products, and the pros and cons for different contexts. And I think that probably as we as our experiences with other sorts of regulatory responses, you’re unlikely to have one model that will be perfect in all circumstances, but thinking about the very sort of spectrum of models will help policymakers and member states as well as civil society, and others to make more educated and informed decisions, as well as to identify areas where we don’t yet know the answers. Where do we need more research? Where do we need more dialogue and consultation?
Question time not captured (over time)
Side Event: Emerging research on psychedelic therapies and their implications for policy
Organised by the UNODC Research and Trend Analysis Branch with the support of the International Society for the Study of Drug Policy
14.10pm CET Thursday 16th March 2023
The side event will explore the current clinical research of psychedelic compounds in treating a range of
mental health conditions. Ongoing Phase 2 and 3 trials in the United States and Europe using MDMA,
psilocybin, and other psychedelics suggests that emerging therapies might be available to patients by
the end of the decade. Presently, several jurisdictions are considering alternative policies aimed at making these compounds more accessible. This event will describe some of the ongoing clinical research in using psychedelics to treat depression, anxiety, post-traumac stress disorder, and other conditions
and what that means for related policy.
Chair: Angela Me, Chief, Research and Trend Analysis Branch, UNODC
So our question was – what are the new research issues that we want to discuss – what’s happening from the medical research on use of psychedelics, but on the perception of what psychedelics might be good or not good for? From our research perspective – what is the implication of the evidence that we have now, for drug policy? The perception is similar to what has happened for cannabis – with psychedelics, it’s faster than the research side. So – where are we in the research?
Gabriella Gobbi, Professor, McGill University
Research sponsored by Canadian Government. Psychedelics have been used for 3000 years. In the western culture, psychedelics more popular in 1938 when Hoffman synthesised LSD. Also, psilocybin was available for research. From this time, until 1970, there was a lot of psychedelic research, when the US scheduled many psychedelics.
Slide – Serotonin Hallucinogens
Tryptamine – Psilocybin and psilocybin (magic mushrooms), DMT (ayahuasca), Lysergamine (LSD) ergot, Phenethylamine (Mescaline) peyote.
MDMA – not a serotonergic – pure synthetic, synthesised in 1912 – empathogenic.
Recent studies:
- LSD plus psychotherapy in anxiety disorders – complex study, started with placebo. You can see a clear reduction in anxiety.
- Psilocybin psychotherapy in AUD – decrease in % of heavy drinking days.
- Psilocybin plus psychotherapy in major depression – only two doses of psilocybin were effective compared to daily medication of Escitalopram.
- MDMA + psychotherapy for PTSD – able to decrease significantly the symptoms of PTSD. First clinical trial
We’re really interested in understanding how psychedelics as medication work. E.g. using low does vs high doses. LSD mechanism of action has some similarities to Prozac, and LSD increases neuroplasticity.
Slide – recent regulations of psychedelics in the world
Matthew Johnson, Johns Hopkins University
Focusing on psilocybin and the effects on mental health. Conflicts disclosed.
Psilocybin in >200 mushroom species. Classic psychedelics – psilocybin, LSD, mescaline, DMT. Ancient uses of psilocybin date back to a cave painting in Algeria 9000 years ago. 1940-70s – promising findings for cancer-related distress and alcoholism, I have focussed a large portion of my work on abuse liability and risks (2008 & 2018). I have researched bad trips. One risk that isn’t there with classic psychedelics – not addictive (but can be abuse). These treatment models don’t require daily dosing. They are mostly based on psychedelic therapy model where a physician available in case of emergency.
So there’s this construct called mystical experience that has roots going back to William James. It sounds a little like it’s referring to the supernatural but it really just refers to the psychological experience that one has. Sort of the mystical experience refers to a number of things but primarily having a sense of unity such as feeling it one with the universe or one with the rest of humanity and unveiling a sense of transcending time and space and some other constructs but when we look at that we do see this relationship between decreased anxiety and depression six, five weeks later, being correlated with the degree of mystical experience as measured in self-report at the conclusion on that session day where people received it.
It’s the nature of the experience, very similar results by our colleagues at New York University published at the same time in some previous research by trying to grow up at UCLA, now moving into depression outside of cancer, some early promising results by the Imperial College Group published in 2016, showing reductions in depression for at least three months. So similar results of randomised trial. So you see these data most another large trial, over 20 patients large reductions in depression, for addiction. I’ll skip past this historical research, but we reach out results with smoking cessation with very high levels. As abstinent six months after our treatment with three sessions of psilocybin, which really looks much larger than existing treatments.
In our pilot study, mystical experiences be related to the outcomes. We’re almost done with a randomized study compared to make a team patch and right now, we’re seeing for over 60 people about a doubling of success for year out, compared to nicotine patch. We’ve gotten a US federal grant to continue that research in the US. Very similar line of research by our colleague, Michael Bolden acutes at NYU. We think there’s something very interesting trans diagnostically connecting these disorders. People seem to be mentally stuck in a self-optimal way of being involved these disorders. And so it seems that the commonality is that we need to figure out the mechanisms or so but these sessions have this profound ability and some people to get them unstuck and to get them out of that sub optimal routine.
Jan Ramaekers, Professor, University of Maastricht
Psychedelics in same chemical club as psilocybin – DMT – long psychedelic experience (depending on the dose you take. Can be complicated in hospital settings. DMT and 5-MeO-DMT. Onset of the experience can be very fast. Entire experience can last 10-20 mins. Both are fast acting, short duration.
Ayahuasca – comes from the Amazon for spiritual and religious purposes. Complicated in terms of its constitution. It is a psychedelic and can be used to alter and improve mental health. Comes from observational studies – it’s mostly used outside of clinics (in Europe, US, everywhere) where you can pay fees to drink Ayahuasca. After the exposure to ayahuasca, we’ve seen reductions in depression (within 24 hours). Not everyone has a response though – some non-responders.
Researchers/small biotech companies have produced a synthetic version of DMT to treat symptoms of depression. D’Souza – published in 2022. Looking at a low dose and a higher dose of DMT. More recently – top line results published from Small Pharma – treating with an active dose of DMT or placebo – 30% of those in active group when into remission, only few in the placebo group. These people then went into an open label study and then 60% went into remission. In D’Souza study, there was some minimal psychotherapy.
Did some fieldwork with 5MEO DMT – participants volunteered to inhale toad venom – here were saw improvement in mental health outcomes. However, these were health volunteers, not patients. Measured magnitude of psychedelic experience – higher the dose, higher the magnitude of psychedelic experience – and then the stronger the decreases in symptoms.
Reckweg et al 2021 slide – shows that it is very short acting, could do multiple doses. We didn’t know the recreational dose, so started very low. Everybody reached the peak experience.
Discussant: Rosalie Liccardo Pacula, Professor, University of Southern California
I’m convinced there is opportunities for different doses for different substances. So when we talk about psychedelics and the policies towards psychedelics, I think it would be better to think about which psychedelic because as we heard from the three presenters, there are some differences in terms of what they do in our bodies in the light and a level the clinical evidence differs when you’re thinking about changing policies, because this is what the debate is about.
When you’re talking about medicine, there’s a typical medical process that requires a certain body of products. The most samples that are shown here have relatively small samples. We think of those as more like clinical trials or getting quotes. What what’s, what’s unique about this is these are studies that are being published in a really good strong scientific journal. This is different than cannabis quite honestly, cannabis while there is still the same level of studies that love the evidence of the science publication wise where it’s published is not as strong a signal about the robustness of the spine. Here, the science since there, it’s getting there and we’re moving to those next stages. If the decision is to make it available medically to change policy, so it’s available medically. That has tremendous gains for for our patients. There is recommended dosing, it’s highly regulated and the product that is delivered has advantages to a product in the case of the psychedelics that in many cases, is a complaint. Relating plants. We have very good agencies and all of our countries, that Department of Agriculture, they’re very good at regulating what the environment is around the plant to make sure the plant thrives.
But those agencies aren’t as good at understanding what’s inside of the plant and what that does to our bodies. That science is usually held in a different regulatory body which is where medicine we have we move a policy forward if we aren’t thinking about the regulatory environment to set up a system that protects the consumer, whether they’re a medical consumer, or a non-profit. That part of what you want to think about in these debates. The other thing that you want to think about is whether it’s appropriate to schedule coming from the Global North. My bias I will be just upfront is to go through a medical route where it is a known product because of the North access to those medications isn’t as difficult as a campaign that needs to be considered when thinking about the international treaties and whether or not to be included in those treaties. It was part of the debate with Canon just a few years ago. It was a plan it was a psychedelic in the US at the schedule two drug war and make available in the for medical purposes already through our standard medical normals. That’s because it’s not scheduled internationally.
We do have lots of nations experimenting. It goes beyond both Canada and a few US states. In fact, in the US, we have a special focus program for MDMA already going so each drug clinically, in terms of policy is being treated strategically because of evidence of scientific body kindness. We go to that international forum and say, what is the best treatment for these drugs we really need to be thinking about access to what looks to be very promising medication and what vehicle through which that can be made available. The rules we’ll get a five internationally will set the rules within each country and how they’re allowed to count and that can have implications for local us. Thank you
Caitlin Hughes, Incoming President of ISSDP
My role is to think about this in terms of legal and regulatory issues that we think about as we think about converting the science into rolling out these policies in different countries. What I wanted to know is that, as our first speaker outlined, that there have been a few different countries that have started to put into practice some different models for accessing substances, whether that’s for describing or different substances. And I think what’s interesting is that already you can see some quite different types of models. So for example, if you have to think about Denver, Colorado, which in May 2019 has decriminalized psilocybin. Here the initiative is very much about reducing prosecution to people who are present, but also enabling people to grow their own psilocybin. So that’s one type of model, then we have Oregon. It’s a different type of model again, because here for Oregon, they legalised psilocybin but they have also rolled out a range of fairly stringent outside medical conditions and systems under which it needs to be used. There’s manufacturing requirements. And there’s requirements for testing purest purity potency, there’s also no requirement that the product will only be able to be purchased, possessed and consumed at licensed facilities using a specially manufactured products and under the supervision of trained facilitators that have returned to Australia where I live. Last month the Australian Therapeutic Goods authority made the decision that from the first of July this year, medicines containing both psilocybin as well as MDMA can be prescribed for a number of conditions. The range of conditions here is more limited. It’s only for treatment resistant depression, and PTSD. In this instance, prescribing will be limited only to psychiatrist and only two psychiatrists who have obtained permission through authorized prescriber scanning and so that they can control the circumstances under which people have assets. So it’s a very medicalized model again. So policies differ on in a number of way because one is about what medical conditions are which access is afforded. Another is how is the drug obtained? Do people grow themselves after they had to obtain from the black market? Do they get it from a new white market? Is it a medical is a synthetic product? There’s also been questions about the context under which one we use. Is it in a very medicalized setting? Is it in open status as we’ve heard in many parts of Latin America, or is it in someone’s own personal use and then you’ve got questions about the level of medical oversight about the sessions. I think there are still further themes that we’ve seen for the presentation today. That for each substance, it’s probably likely to require somewhat of a different model regulatory response. I think more broadly, what we’ve learned throughout looking at medical cannabis, as well as looking at models of decriminalization or legalization of cannabis, is that the design choices really do matter. And so I think it’s probably we’re probably at a sort of tipping point to start to think about different types of models, or access to these products, and the pros and cons for different contexts. And I think that probably as we as our experiences with other sorts of regulatory responses, you’re unlikely to have one model that will be perfect in all circumstances, but thinking about the very sort of spectrum of models will help policymakers and member states as well as civil society, and others to make more educated and informed decisions, as well as to identify areas where we don’t yet know the answers. Where do we need more research? Where do we need more dialogue and consultation?
Question time not captured (over time)