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Sustained subjective benefits of LSD for the treatment of end-of-life anxiety

December 6, 2021 / Articles, End of Life Anxiety, LSD, Publications, Research / By

LSD_clinical_trial_bottle_small

Earlier, we reported on the first study with LSD in human subjects in more than forty years, conducted in Switzerland by Peter Gasser and his team. A follow-up of this study [1], based on qualitative interviews with participants, indicates lasting positive outcomes.

The original double-blind, placebo-controlled study was carried out on a sample of twelve subjects, nine of which went on to complete the full course of the study, including the 12-month follow-up. The participants, all terminally ill, underwent 6-8 non-drug psychotherapeutic sessions and two LSD experiences conducted by a co-therapist dyad. The four subjects who initially received the active placebo of 20µg of LSD were offered the possibility to take two full experimental 200µg-doses of LSD at the end of the actual study, an opportunity that was taken by three of them, who were subsequently included in the qualitative interviews.

All subjects had previously displayed significant anxiety and/or depression related to their life-threatening health situation. All of them reported considerable long-term benefits, among which are reduced anxiety, less fear of death, and an improved quality of life. Interestingly, most of them also reported positive changes in personality, which could be a subjective confirmation of the quantitative measures of trait anxiety (as opposed to state anxiety) that were reported. These trait measures dropped significantly after the LSD sessions, and remained low at the 12-month follow-up [2].

In subjective reports of the LSD sessions, participants described facilitated access to emotions and catharsis. Facing a short life prognosis, they reported that LSD intensified and allowed expression of associated emotions. The interviews suggest the patients benefited from this intensified emotional experience. LSD also enabled them to view themselves and their difficult situation in a new, broader perspective. “Dying is as usual or unusual as life itself,” said one patient. “I simply have to familiarize myself with the idea and the process.” The patients also reported drastic shifts in emotions during or between the two sessions, usually beginning with ‘negative’ feelings related to their life situation, such as anxiety, depression and hopelessness. This reportedly negative emotional state transformed into a positive one, felt with an intensity never experienced before and lasting for at least one year after the sessions. Although they were facing ongoing severe somatic diseases, none of the participants reported any adverse effects from the psychedelic sessions.

Another interesting aspect is the approach that was chosen. Two different approaches emerged from the early research with LSD between the 1950s and the 1970s. In psycholytic therapy, used mainly in Europe, patients underwent a high number of psychoanalytically oriented psychotherapeutic sessions with low to medium dosages of LSD (50-100 µg). The psychedelic approach, on the other hand, aimed to elicit mystical or peak experiences in patients by administering them high doses (200-500 µg) in a limited number of sessions. This latter method was more frequently used in the United States, and up to now, it is the only approach that was used in the treatment of end-of-life anxiety.

In the Swiss study, the approach was very much akin to the psychedelic method, however staying on the low side of the dosage range. The setting was also somewhat looser than in the traditional psychedelic approach, where the subject kept on eyeshades most of the time while listening to music through headphones. Most of the resulting experiences could be described as ‘peak experiences’, but do not match the criteria for full mystical experiences. These two types of experiences can be quite similar. Ego boundaries are loosened in peak experiences, but don’t dissolve completely as in mystical experiences. Intellectual functions also stay intact to a greater degree, which allows for a higher degree of interaction between subject and guiding therapists than in the traditional psychedelic approach. These peak experiences seem to be the main psychological mechanism of action involved, much more so than the cognitive and psychodynamic experiences that are also frequent as a result of LSD administration.

The Swiss study’s approach certainly has advantages, one of which being that it seems to normalize the results for all participants. In past studies with psychedelics for end-of-life anxiety, conducted during the first era of psychedelic research, the typical outcome would show a dramatic improvement in about one-third of the subjects, a moderate improvement in another third, and no significant changes in the remaining third [3]. In the present study, remarkably, every single patient experienced significant improvement, although none reported ‘dramatic’ effects. This result certainly warrants further study, especially in light of the development of different therapeutic approaches to be used in psychedelic therapy.

 
[1] Gasser, P., Kirchner, K., & Passie, T. (2014).
[2] Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014).
[3] Kurland, A.A. (1985).
 
References
Gasser, P., Kirchner, K. & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology, 29(1), 57-68. [Abstract]
Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease, 202(7), 513–520. [Abstract]
Kurland, A.A. (1985). LSD in the supportive care of the terminally ill cancer patient. Journal of Psychoactive Drugs, 17(4), 279–290. [Link to full text]

The potential religious relevance of entheogens

December 6, 2021 / Articles, Publications, Religious studies, Research, Spirituality / By

At least since William James, scholars of religion have wondered if mystical experiences induced by means of chemical substances are similar or identical to, and have the same value as, naturally occurring ones. Lengthy debates ensued throughout the 20th century, fuelled in part by scientific research such as the classic Good Friday experiment conducted in 1962 by Walter Pahnke. As the discussion on these experiences induced by external means, and their implications, goes on today, Zygon: Journal of Religion and Science (vol. 49, no. 3) has devoted a section of its September 2014 issue to the potential religious relevance of entheogens [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1].

In the first of four articles, Ron Cole-Turner focuses on the recent psilocybin research at the neuropsychopharmacology group at Imperial College London by Carhart-Harris et al. (2014), whose findings depart from the view that psychedelics increase neural activity in the brain. On the contrary, the researchers found that psilocybin decreases neural activity in the default mode network [2], which they suggest is the “seat of the ego”. This result is “highly suggestive in terms of how psilocybin might function in the brain to “occasion” mystical experience,” Cole-Turner writes. The author however takes issue with the “pejorative” label of “magical thinking” the London researchers associate with the subjects’ supernatural interpretations of their experiences. Here, he draws a line between the London research team and the team at Johns Hopkins [3] that also studies psilocybin. For the former, mystical quality seems to be an unwanted side-effect, writes the author, while for the latter it is the very focus of research, and a desirable feature. “More than science is at play here, and more than religion is at stake”, Cole-Turner concludes, wondering what we will make of what we are about to discover.

In the second article, William Richards, who worked with Walter Pahnke in the 1960s and has himself worked on recent psilocybin research, starts by stating that psychedelics “provide two new factors critical for religious scholarship […], namely potency and reliability”. This means that meaningful experiences can be safely induced in most subjects, and the author notes that over 200 persons have now safely received psilocybin within the framework of the Johns Hopkins psilocybin research. He goes on to define mystical experiences and distinguishes them along three binary dimensions: complete and incomplete, unitive and personal, and internal and external mystical experience. His research [4] has shown that both aspects of these dimensions are not mutually exclusive, as some scholars of religion have argued, and can be experienced by the same person. Richards lays out two avenues of potential interdisciplinary research for scholars of religion: the study of religious groups that use entheogens in a sacramental way, and collaborations with colleagues from other fields in the design of interdisciplinary studies with entheogens.

The Santo Daime religious movement, which uses the Amazonian brew ayahuasca as its main sacrament, is the focus of the third article, written by G. William Barnard. In the first, introductory part, the author distinguishes between the productive and transmissive theories of the brain. In the latter, consciousness pre-exists the brain, which serves as a transmitter to the human body and mind. The productive theory, on the other hand, posits that consciousness is altogether produced by the brain. If we were to take the transmissive perspective, then mystical or religious experiences are not just “the hallucinatory byproducts of cerebral malfunctions caused by the chemical activity of these substances”, the author writes. In the second part of the article, Barnard goes on to sketch the history and main theological tenets of Santo Daime. He suggests that “[Huston] Smith’s [5] desire to see the birth of a modern day mystery school that revolves around the sacramental use of entheogens has, in fact, been fulfilled”, citing the Native American Church, and the Brazilian União do Vegetal religious group as other examples. In Barnard’s view, one of the primary reasons for Santo Daime church members to uphold their strict discipline is the extent of spiritual transformation and physical healing their practice provides.

In the last article, Leonard Hummel underscores the importance of lasting effects from mystical experiences, and notes that the Johns Hopkins study [6] did look for and found desirable long-term effects in the lives of participants. Hummel contends that the validity of drug-induced mystical experience is hardly ever questioned anymore, despite criticism that research focuses on the individual religious experience (“a momentary sense of wow”) rather than on its repercussions in the community. In his view, these criticisms are not in line with the reality of either ongoing (clinical) trials (which include questionnaires about the effects on the community practices of participants), or of existing religious communities such as Santo Daime or peyote churches. He also hypothesizes that the Council on Spiritual Practices intends to give rise to recognized entheogen-based religious communities in the US. Hummel does not envision, however, the use of entheogens in Christian communities in the US, underscoring – among other things – possible health hazards, due to the possible lack of an adequate setting. Therefore the author concludes that the administration of entheogens had better remain confined to a therapeutic setting.

All articles appear in the September edition of Zygon: Journal of Religion and Science (volume 49, no. 3), The Potential Religious Relevance of Entheogens.

 
[1] “Entheogen” is a synonym for “psychedelic” that is often used in a religious context. Literally, it means a compound that “generates the divine within”.
[2] The default mode network is a network of brain areas that is mainly active in a state of rest, when attention is more focused inwards than outwards.
[3] See for example Griffiths et al. (2006).
[4] Richards (2008).
[5] Huston Cummings Smith is a well-known religious studies scholar from the United States.
[6] Griffiths et al. (2006).
 
References
Barnard, G. William (2014). Entheogens in a Religious Context: The Case of the Santo Daime Religious Tradition. Zygon: Journal of Religion and Science, 49(3), 666-684. [Abstract]
Carhart-Harris, Robin L., Robert Leech, Peter J. Hellyer, Murray Shanahan, Amanda Feilding, Enzo Tagliazucchi, Dante R. Chialvo, and David J. Nutt (2014). The Entropic Brain: A Theory of Conscious States Informed by Neuroimaging Research with Psychedelic Drugs. Frontiers in Human Neuroscience 8. doi : 10.3389/fnhum.2014.00020 [Abstract]
Cole-Turner, Ron (2014). Entheogens, Mysticism, and Neuroscience. Zygon: Journal of Religion and Science, 49(3), 642-651. [Abstract]
Griffiths, R. R., Richards, W. A., McCann, U. & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance, Psychopharmacology, 187, 268–283. [Abtract]
Hummel, Leonard. By Its Fruits? Mystical and Visionary States of Consciousness Occasioned by Entheogens. Zygon: Journal of Religion and Science, 49(3), 685-695. [Abstract]
Richards, W. A. (2008). The Phenomenology and Potential Religious Import of States of Consciousness Facilitated by Psilocybin. Archive for the Psychology of Religion, 30, 189-199. [Abstract]
Richards William A. (2014). Here and Now: Discovering the Sacred with Entheogens. Zygon: Journal of Religion and Science, 49(3), 652-665. [Abstract][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Ibogaine: useful in treating addiction to non-opioids?

December 6, 2021 / Addiction, Articles, Iboga / Ibogaine, Publications, Research / By

iboga508It has been known for some time that ibogaine can probably help in the treatment of drug addiction. But up until now researchers focused primarily on the addiction to opioids like heroin and morphine. A group of scientists in Brazil found out that ibogaine might also help against addiction to alcohol, cannabis and cocaine, implying a wider range of potential therapeutic applications.

Treating drug dependence can be hard. Conventional therapies often are lengthy and costly. Nowadays the increased interest in the potential of psychedelics in the battle against addiction has urged new investigations. Several studies on the use of LSD and psilocybin for this purpose have been published [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1]. Ibogaine is another psychedelic that has gained the attention of scientists. This is an alkaloid that can be found in the root bark of the Tabernanthe iboga plant, growing in West central Africa. As early as 1962 the substance was used in trials to overcome heroin addiction. But further investigation was made difficult by a statutory ban in many countries. In Brazil however, ibogaine is not an illegal substance, allowing research to continue. A group of scientists from the University of São Paulo, led by Eduardo Schenberg, retrospectively evaluated data from a private clinic in Curitiba, which treated patients with pure ibogaine HCl in a professional environment and as part of a larger psychotherapeutic program [2]. The patients in the study were addicts to alcohol, cannabis, cocaine, and/or crack cocaine. The researchers concluded that 61% of these patients were still abstinent after five to eight months, and that none of them experienced long-lasting negative side effects. Repeated sessions (two or three times) appeared to be especially effective.

Using ibogaine in the treatment of drug addiction is not without risks however. The substance can cause serious arrhythmia, which has led to several fatalities in the past. But according to Schenberg et al., most of these cases were probably due to a pre-existing heart disorder (e.g. “long-QT-syndrome”, a condition causing severe irregular heartbeat). Moreover, the ibogaine or iboga extracts in those cases were often used without quality control and without the supervision of trained and qualified medical staff. Using other psychoactive substances and certain prescription drugs shortly before the ibogaine ingestion can also cause adverse effects. For that reason, the clinic in which this study took place implemented a protocol to ensure that patients are abstinent at least thirty days before the ibogaine is administered. If this is observed and sessions are accompanied in a professional way, then ibogaine can probably be a good aid in the treatment of addiction, according to the researchers. They admit however that more research is necessary, also into the potential adverse effects of ibogaine on the heart.

 
[1] Johnson et al. (2014) and Krebs & Johansen (2012)
[2] Schenberg et al. (2014)
 
References

Schenberg, E. E., de Castro Comis, M. A., Rasmussen Chaves, B. & da Silveira, D. X. (2014). Treating drug dependence with the aid of ibogaine: A retrospective study. Journal of Psychopharmacology, 28(11), 993-1000. [Abstract]
Krebs, T. S. & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(11), 994-1002. [Abstract]
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983-992. [Abstract][/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Online questionnaire about the use of Salvia

December 6, 2021 / Articles, Publications, Research, Salvia / Salvinorin A / By

OLYMPUS DIGITAL CAMERADid you ever use Salvia divinorum? Researchers at Harvard University are eager to know what you experienced. In a completely anonymous online questionnaire you will be asked questions about your use, experiences, and some personality characteristics. The outcomes will be used for a scientific study. Participation is without any obligations, and no personally-identifiable information will be collected. Answering all questions will approximately take 45 minutes to 1 hour. The results of this study will be published in a renowned scientific magazine. Would you like to share your Salvia experience(s) and contribute to science? Then this is your chance!

Click here to participate.

Special issue about psychedelics in 'The Psychologist'

December 6, 2021 / Articles, Interviews, Publications, Research / By

The British Psychological Association recently published a special issue of their accompanying journal The Psychologist (September 2014, vol. 27) devoted to the rising popularity of research into psychedelics. This is the first time such a lengthy publication, illuminating the intricacies of the psychedelic experience, has appeared in the journal.

David Nutt claims, in the first article of the issue, that the scientific disinterestedness of the past can be explained by society’s attempt to deny psychedelics their “value and importance” in the study of altered states for moral reasons. The political reasoning is the following one: how can we not but condemn research into psychedelics if this poses the risk that it would legitimize recreational use? However, Nutt asserts that despite the possible societal risk “(t)he failure of the scientific community, particularly neuroscientists, to protest the denial of research on hallucinogens is one of the most disturbing failures of science leadership in the past century, and it must be rectified. Psychologists and other neuroscientists must demand the right to study these drugs” (2014).

Many neuroscientists did not wait for Nutt’s summoning to start unraveling the relationship between psychedelic drugs and the human brain. In How do psychedelics work on the brain? (the second article) Carhart-Harris, Kaelen and Nutt (2014) describe the psychedelic experience, starting at the neurotransmitter level and ending at the neuronal large-scale systems of the brain. The obvious question for psychology (as is stated in the title of the special issue) is whether the neuronal level can tell us anything about the psychedelic experience that is within our field of meaning or, as Jameson puts it, our “cognitive mapping” (1991). The title of the special issue suggests that human psychology, by adopting neuroscientific knowledge, can do just that.

In the third article, Vaughan Bell (2014) opposes this approach and asks a different question: what can we learn from the ways in which other societies approach hallucinogenic drugs? Bell asserts that “drug-induced hallucinations are often discussed as if they can be entirely understood in terms of their chemical action in the brain”. In Bell’s view it is not the brain, but rather culture and the relationship between the individual and her social context where the real magic happens.

The fourth article, by Henry David Abraham (2014), connects the three previous ones by describing the author’s investigations into hallucinogen persisting perception disorder (HPPD). Here Abraham gives a phenomenological reading and tries to describe the complex dynamic between the neuronal and the psychological dimensions of HPPD.

Charles Grob, Ira Byock and Erica Rex, in the fifth article Viewpoints: Experiences of hallucinogen treatment (2014), extend the view posited by Abraham and give an account of the exciting ‘new’ realm of psychedelic treatment and psychological assistance. “Multiple participants”, says Byock, “report not mere alleviated anxiety or depression, but also an enduring sense of well-being. Some expressed feeling at peace, grateful for their lives, forgiving toward others and toward themselves and being less fearful and more confident about the future”. The treatment intervention for “existential anxiety” proposed by Grob (2014) is seen as just one of the many possible applications of psychedelic substances.

All articles appear in the September edition of The Psychologist (volume 27, part 9) “A brave new world for psychology?”

 
References
Abraham, H. D. (2014). When the trip doesn’t end. The Psychologist, 27(9), 670-673.
Bell, V. (2014). Cultures of chemically induced hallucinations. The Psychologist, 27(9), 666-669.
Carthart-Harris, R., Kaelen, M., & Nutt, D. (2014). How do hallucinogens work on the brain? The Psychologist, 27(9), 662-665.
Grob, C.S., Byock, I.R., Rex, E. (2014). Viewpoints: Experiences of hallucinogen treatment. The Psychologist, 27(9), 676-679
Jameson, F. (1991). Postmodernism, or, the cultural logic of late capitalism. Durham, NC: Duke University Press.
Nutt, D. (2014). A brave new world for psychology? The Psychologist, 27(9), 658-661.

Psilocybin against tobacco addiction

February 7, 2022 / Addiction, Articles, Mushrooms / Psilocybin, Research / By

A positive treatment perspective for one of the current most persistent and deadliest addictions comes from a psilocybin-assisted smoking cessation study carried out at the Johns Hopkins University School of Medicine in Maryland, USA [2].

The form of treatment consisted of up to three psilocybin sessions additional to cognitive behavioral therapy. Twelve out of fifteen participants (80%) succeeded in quitting their habit after this treatment for a minimum of six months [3]. Participants experienced an increased faith to effectively deal with the addiction, a heightened spiritual awareness and an uplifted state of overall well-being. An interesting finding was that, although three participants didn’t succeed in quitting, this group turned out smoking less cigarettes a day six months after the beginning of the treatment.

Because of the study design lacking a control group, it is not (yet) possible to solely ascribe the therapeutic effect of the treatment to the characteristics of psilocybin. Nevertheless, these results promise a better treatment perspective for psilocybin combined with cognitive behavioral therapy than for regular treatment options. The success rate in this study being 80%, compared to 25% to 34% when treated with buproprion or varenicline respectively [4], or compared to around 50% when treated with a combination of bupropion, nicotine replacement, and intensive cognitive behavioral therapy [5][6]. More scientific studies would be necessary in order to understand the full potential of treating smoking addiction with psilocybin or other pharmacons that have their mechanism of action on the 5-HT2A-receptor.

The idea of using psychedelics to fight addiction is nothing new. In the 50s and 60s there were a lot of research projects focusing on the therapeutic potential of these compounds. The interested reader might want to take a look at a meta-analysis by Teri Krebs (2012), which, based on six of these studies, concluded that the treatment of alcoholism using LSD seemed to be very effective.

[1] World Health Organization (2011)
[2] Johnson, Garcia-Romeu, Cosimano, & Griffiths (2014)
[3] The notion should be considered that several participants indicated to have a relapse period between the last psilocybin session and six month follow-up, but that they were able to correct it themselves and continued as non-smokers until follow-up.
[4] Gonzales et al., 2014; Jorenby et al., 2014
[5] Hall et al., 2009; Killen et al., 2008
[6] Success rates are based on 7 day point prevalence abstinence measures of smoking behavior. Gathered by self-report and urine- and breath analyzes.

References
Gonzales, D., Rennard, S. I., Nides, M., Oncken, C., Azoulay, S., Billing, C. B., … Reeves, K. R. (2014). Varenicline, an ␣ 4 ␤ 2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for Smoking Cessation, 296(1), 47–55.
Hall, S. M., Humfleet, G. L., Muñoz, R. F., et al. (2009). Extended treatment of older cigarette smokers. Addiction, 104, 1043-1052
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology (Oxford, England), (September). doi:10.1177/0269881114548296
Jorenby, D. E., Hays, J. T., Rigotti, N. A., Azoulay, S., Watsky, E. J., Williams, K. E., … Reeves, K. R. (2014). Efficacy of Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking CessationA Randomized Controlled Trial. JAMA, 296, 56-63.
Killen, J. D., Fortmann, S. P., Schatzberg, A. F., et al. (2008). Extended cognitive behavior therapy for cigarette smoking cessation. Addiction, 103, 1381-1390.
Krebs, T. S., & Johansen, P.-Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology (Oxford, England), 26(7), 994–1002. doi:10.1177/0269881112439253[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Johns Hopkins "Bad Trip" Survey

December 6, 2021 / Articles, Other subjects, Publications, Research / By

badtripsgraphic508The Psilocybin Research Team at Johns Hopkins needs your help! To study the complex, and often challenging experiences usually referred to as ´bad trips´, the Psilocybin Research Team is conducting an anonymous, web-based survey into this very phenomena. If you’ve ever had such an experience, they would greatly appreciate it if you participate. Also if you know anyone that has had such an experience and would be interested in participating, don’t hesitate to pass on the link.

Please participate and share: http://www.shroomsurvey.com

BACKGROUND: As you may remember, last year we conducted an internet survey characterizing challenging experiences (so called “ bad trips”) after taking psilocybin. The results of that survey have been quite interesting and will result in two or more publications. As part of the analysis of data from that survey, we have developed a second version of the survey that should permit the final development of a psychometrically rigorous Challenging Effect Questionnaire that we hope will make a significant contribution to the scientific understanding of psilocybin. This work complements our published and ongoing work validating a questionnaire assessing psilocybin occasioned mystical experiences.

PTSD and MDMA in the ‘picture’

December 6, 2021 / Anxiety disorders / PTSD, Articles, MDMA, Publications, Research / By

a5_ptsd_508With an upcoming fMRI study in the United Kingdom, an attempt is being made to outline the neurobiological mechanisms that are hypothesized to underlie the favorable outcome of MDMA-assisted psychotherapy in posttraumatic stress disorder (PTSD).

Earlier studies found that after just a few treatment sessions with MDMA in addition to psychotherapy, there was a significant short [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][1] and long [2] term improvement of PTSD symptomatology in patients that were resistant to regular psycho- and/or pharmacotherapy [3]. Up to today, not much is known about the factors that contribute to the success of this form of treatment. Several researchers suggest that MDMA, o.a. by temporarily reducing fear and by easing interpersonal contact, facilitate the therapy on a psychological level [4], but about the neurobiological foundations remains to be speculated.

By using fMRI, dr. Ben Sessa and his research team at Cardiff University will try to image the manifestation of MDMA in PTSD patients. To capture the effects of the compound in isolation, the patients will not receive any psychotherapy during this study.

The research proposal is currently waiting for approval of the Committee of Ethics.

 
[1] Mithoefer, Wagner, Mithoefer, Jerome, & Doblin (2011)
[2] Mithoefer et al. (2012)
[3] A similar study from Oehen, Traber, Widmer, & Schnyder (2013) did not reach significance on the primary measurement (p = .066), a diagnostic tool to assess PTSD symptomatology, though at a subjective level the patients indicated to have some relief from their former complaints. Bouso et al. (2008) couldn’t draw any firm conclusions on their data of the first MDMA-assisted psychotherapy study in PTSD, due to a sudden unexpected cancellation of the study and the consequencing small study sample.
[4] Bouso, Doblin, Farré, Alcázar, & Gómez-Jarabo (2008), Mithoefer et al. (2011), Oehen et al. (2013)
 
References
Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. A., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Journal of Psychoactive Drugs, 40(3), 225–36. doi:10.1080/02791072.2008.10400637
Mithoefer, M. C. M., Wagner, M. M. T., Mithoefer, A. A. T., Jerome, L., Martin, S. F., Yazar-Klosinski, B., … Doblin, R. (2012). Durability of improvement in posttraumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology (Oxford, England), 27, 28–39. doi:10.1177/0269881112456611
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of psychopharmacology (Oxford, England) (Vol. 25, pp. 439–452). doi:10.1177/0269881110378371
Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2013). A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). Journal of Psychopharmacology (Oxford, England), 27(1), 40–52. doi:10.1177/0269881112464827[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Psychedelic Research 2.0 – Part 1

December 6, 2021 / Articles, Background articles, Publications, Research / By

After a 20 year study-shutdown on psychedelics, a second wave of interest in the nature and applications of these compounds has engulfed the international research community and rendered a wealth of studies. To help you find your way in the forest of exciting information, this two-part series of articles provides an overview of contemporary (1990 – present) psychedelic research themes. Part 1 will focus on more fundamental research, while part 2 will focus on clinical research.

Part 1: Fundamental psychology

Before getting to the exciting part of this article where we will dive into studies that are done in the psychology field, let’s start with some definitions and explanations. According to the American Psychological Association (APA, 2014), psychology is:

“… the study of the mind and behavior. The discipline embraces all aspects of the human experience — from the functions of the brain to the actions of nations, from child development to care for the aged. In every conceivable setting from scientific research centers to mental healthcare services, “the understanding of behavior” is the enterprise of psychologists.”

For the sake of clearance, conciseness and convenience, the studies with a psychological character will be discussed in two separate articles with a distinction being made between fundamental and clinical research. This first part of the series of psychedelic research themes 2.0 will provide an overview of fundamental research. Fundamental research aims at exposing the general processes that underlie the phenomena of interest and does not necessarily have a direct application. Clinical research tends to be of a more practical nature, since it is primarily aimed at understanding a particular disease or maladjustment and searching for an adequate cure. Though these classes are treated as distinct in this series, please keep in mind that there is a considerable overlap and synergy between the two.

In the fundamental corner, roughly four psychedelic research themes that have been under the microscope for the past twenty years will be distinguished in this article. These concern matters related to cognition, creativity, personality and psychopharmacology.

Cognition

Cognition is a broad term and can be defined in several ways depending on the discipline in which it is used. In neuroscience, cognition is usually considered from the information processing view, explaining human behavior in terms of executive functions. Put simply: there is input (perceptual information), there is output (behavior), and there is something happening in the black box that is known as the brain (executive functions). Cognition usually refers to the total package of processes that is involved in this ongoing cycle of day to day functioning.

Psychedelics exert an acute influence on a variety of these functions, which have been extensively studied with behavioral tasks and neuroimaging techniques. Conclusions about the exact nature of this temporary alteration in cognition have been mixed and even contradictory, which might partially be due to the inconsistency of the study design and substance involved. Amongst others, acute changes in working memory, attention and perception have been described in the literature (for a comprehensive overview, see Passie, Halpern, Stichtenoth, Emrich, & Hintzen, 2008; Bouso, Fábregas, Antonijoan, Rodríguez-Fornells, & Riba, 2013). The fine-tuning of the knowledge that is currently available about the relation between psychedelics and cognitive skills goes hand in hand with increasing information about receptor binding sites, localization of function and brain connectivity.

More standardized study designs seem to be a necessity to learn more about the causes of the inconclusive evidence.

Creativity

From Nevole’s (1947, as cited in Winkler & Csémy, 2014) point of view “…the normal human way of perceiving and thinking, is just one possibility out of many potential possibilities”. He argues that ‘normal’ perception, thoughts and behavior of an individual are the result of socio-cultural learning. The integration of culturally established norms and values might have an evolutionary purpose, but may put constrain on cognitive processes such as creativity.

In psychological literature, creativity is usually defined in terms of divergent thinking: the ability to generate multiple answers to a set problem (Guilford, 1966). Because the psychedelic experience is characterized by an alteration in perception, changes in emotion and expansion of thought and identity (Sessa, 2008), it is not unthinkable that they could provide an aid to ‘think out of the box’.

During the ’50’s and 60’s, the exploration of creative problem solving under the influence of psychedelic agents was a popular research topic. An interesting article was published by Harman, McKim, Mogar, Fadiman, and Stolaroff (1966) in which the results of an experimental study with LSD were described in a group of men which occupation required creative problem-solving ability. The study consists of objective measures of the effects of LSD on problem solving ability, and subjective ratings of the ability to approach a pre-specified, work-related problem. The latter being one of the strengths of the study, since it permits the participant to consider options in a meaningful context. Some of the mutually agreed on subjective effects of the psychedelic compound seem to correspond to ideas about facilitative conditions under which creativity arises, such as low inhibition and anxiety, the capacity to structure problems in a larger context and high fluency and flexibility of ideation. This article may be considered classic in the psychedelic/creativity domain.

Surprisingly, contemporary research on this exciting topic is scarce, perhaps due to the lack of understanding of the concept of creativity itself, or the methodological challenge to measure it. Results from recent studies that were done with ayahuasca (Frecska, Móré, Vargha, & Luna, 2012) and cannabis (Jones, Blagrove, & Parrott, 2009) suggest the ability of users of psychedelics to produce more original ideas than non-users. It has to be noted here that these are not measures that were taken under the acute intoxication of the substances, but as a comparison between groups that were sober at the time of measurement.

There is a strong need for more studies with intelligent experimental designs in order to understand the source of creativity. The field doesn’t seem to have made full use of the modern imaging techniques, such as electro-encephalography (EEG), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to explore the interaction of acute psychoactive chemistry and creative thinking. Opportunities are waiting here…

Personality

In exploring the interaction between psychedelics and personality, most research follows the nature/nurture discussion of stable versus unstable personality traits. According to Cloninger, Svrakic, & Przybeck (1993) personality can be thought of as a dynamic process between two types of traits. Temperament refers to the more stable, genetically determined set of traits, whereas character can be considered the fine-tuning of personality due to socio-cultural factors.

Evidence in the psychedelic research field suggests that differences exist between users and non-users in both personality domains (Bouso et al., 2012; Grob et al., 1996; Móró, Simon, Bárd, & Rácz, 2011), but this doesn’t answer the question of causality: Are people with a certain set of personality traits more likely to start experimenting with psychedelics, or is there a possibility that these substances can account for shaping personality?

Two recent studies found evidence that certain dimensions of personality which are regarded as stable traits were altered after exposure to ayahuasca (Barbosa, Cazorla, Giglio, & Strassman, 2009) and psilocybin (MacLean, Johnson, & Griffiths, 2011). In the ayahuasca study, differences in the personality aspects reward dependence and harm avoidance were found after repeated exposure to the beverage. A single session of psilocybin seemed to be sufficient to cause a change in the openness to experience dimension.

The results are tentative, but promising: for persons dealing with personality disorders psychedelics might be considered valuable tools. More research on this topic would certainly be encouraged.

Psychopharmacology

Psychopharmacology can be defined as “the study of drugs that affect the brain” (Stahl, 2008). This definition exposes that the psychopharmacologist engages himself in matters related to ‘drugs’, the ‘brain’ and their interaction.

Before diving into contemporary research within this field, it is worth mentioning two pieces of work that are written by Alexander Shulgin (1925 – 2014) – one of the most influential scientists in this field – and his wife Ann Shulgin; PIKHAL, A Chemical Love Story (1991) and TIKHAL, The Continuation (1997). Besides a fictionalized autobiography of these key figures of psychedelic research and a detailed description of over 200 compounds, the books also contain lively and informative subjective research reports from the group of friends in which the substances were ‘tested’. Together, the books cover a wide array of research issues, biochemical information, personal experience and spiritual considerations related to psychedelics.

Back to the 21st century then, in which questions like ‘How do psychedelics manifest itself in the human brain?’ and ‘How does this interaction alter perception and behavior?’ keep persisting. Recent studies have been done to examine the neurobiological mechanisms of ketamine (Hahn et al., 2014), salvia (Johnson, MacLean, Reissig, Prisinzano, & Griffiths, 2011), psilocybin (Muthukumaraswamy et al., 2013) and ayahuasca (dos Santos et al., 2011; Riba et al., 2003; Riba, McIlhenny, Valle, Bouso, & Barker, 2012). Data from substance-by-substance research has led to more holistic neuroscientific theories such as the entropic brain hypothesis, in which a division between two types of consciousness (primary and secondary) is proposed as a way to explain phenomena that can’t be accounted for by a neuroscienfitic perspective on its own (Carhart-Harris et al., 2014).

As substance-by-substance research can provide a stepping stone for theories about human behavior, so can fundamental research complement the understanding of clinical expression. The extensive research that has been done on the role and functioning of the amygdala for example, supports and complements explanations about the effectiveness of antidepressant drugs that are used in the treatment of anxiety and mood related complaints (Crupi, Marino & Cuzzocrea, 2011).

Want to know what this has to do with psychedelics? That, and more will be discussed in the second part of this series: Clinical Research.

 
References
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Barbosa, P. C., Cazorla, I. M., Giglio, J. S., & Strassman, R. (2009). A six-month prospective evaluation of personality traits, psychiatric symptoms and quality of life in ayahuasca-naive subjects. J Psychoactive Drugs, 41, 205–212. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19999673
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Bouso, J. C., González, D., Fondevila, S., Cutchet, M., Fernández, X., Ribeiro Barbosa, P. C., … Riba, J. (2012). Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of ayahuasca: A longitudinal study. PLoS ONE, 7. doi:10.1371/journal.pone.0042421
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Johnson, M. W., MacLean, K. a, Reissig, C. J., Prisinzano, T. E., & Griffiths, R. R. (2011). Human psychopharmacology and dose-effects of salvinorin A, a kappa opioid agonist hallucinogen present in the plant Salvia divinorum. Drug and Alcohol Dependence, 115(1-2), 150–5. doi:10.1016/j.drugalcdep.2010.11.005
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The Therapeutic Potentials of Salvinorin A

February 7, 2022 / Articles, Background articles, Research, Salvia / Salvinorin A / By

Salvia divinorum is a sprawling perennial herb found in the Sierra Mazatec region of Mexico. It has a history of use as a divinatory psychedelic, and has been widely available since the mid 1990s primarily as a smoked herb. Jean Basset Johnson was the first to document its use in 1939. R. Gordon Wasson, better known for his ‘discovery’ of the psilocybin mushroom, continued to document the Salvia divinorum herb and eventually confirmed its psychoactivity on himself in ‘A new Mexican psychotropic drug from the mint family’ published in Botanical Museum Leaflets (1962). Salvia divinorum remained an obscure psychedelic until the mid 1990s when Daniel Siebert, a then still unknown independent researcher, began self experimentation and documented its effects extensively. The Salvia divinorum experience is rather elusive, that is to say its effects seem to vary even more tremendously then other psychedelics, both between people and across sessions.

The molecule, or more specifically; ‘neoclerodane diterpenoid’ (not to be confused with ‘alkaloid’, which always contains a nitrogen atom), behind the dramatic effects of Salvia divinorum is the extremely potent Salvinorin A. “Essentially inactive if taken orally”, says Valdés in ‘Salvia divinorum and the unique diterpene hallucinogen, Salvinorin A’ (1994), “the compound is effective in doses of 200 to 500 mcg when smoked”. This makes Salvinorin A the first documented diterpene hallucinogen and the most potent naturally occurring hallucinogen thus far isolated”. “Salvinorin A”, says Siebert in ‘Salvia divinorum and Salvinorin A: new pharmacological findings’ (1994), “produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity”.

This compound is interesting for many reasons, but recently it has come to the attention of researchers because it acts as a kappa opioid receptor agonist (Roth, 2002). It is the first known compound acting on this receptor that is not an alkaloid. The κ-opioid receptor is a protein and is one of four related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering the perception of pain, motor control, and mood. Wang et al. (2013) demonstrated that “administration of Salvinorin A after hypoxia/ischemia preserves cerebral autoregulation via the κ-opioid receptor pathway”, ultimately presenting a novel opportunity for the prevention of prenatal cerebral hypoxia/ischemia. Fichna et al. (2012) investigated the effect of Salvinorin A (administered intraperitoneally once a day) on acute pain, oedema and formalin-induced persistent pain in mice. The researchers concluded that Salvinorin A exerts analgesic actions and also shows moderate anti-inflammatory effects.

More recently Salvinorin A was used to research the relationship between the claustrum (a sheet of neurons which is attached to the neocortex in the center of the brain) and consciousness. Stiefel et al. (2014) suggests that “the consciousness-altering effects of S. divinorum/salvinorin A are due to a κ-opioid receptor mediated inhibition of primarily the claustrum and, additionally, the deep layers of the cortex, mainly in prefrontal areas”. This finding leads them to believe that Salvinorin A might be new evidence in favour of the ‘Crick and Koch theory’ (1990) which claims that the claustrum is the “conductor of consciousness”, not unlike the philosopher René Descartes claimed for the pineal gland.

Dr. Karl Hanes, researcher at the ‘Cognitive-Behavioural Treatment Centre’ in Melbourne Australia, reported on a treatment-resistant depressed patient (Ms. G) under his care and the management of her symptoms of depression through Salvia (2001). “During a review consultation some seven months after discontinuing cognitive-behavioural therapy”, says Hanes, “Ms. G claimed to have found relief from her symptoms of depression with use of the herb Salvia divinorum. A HAM-D score of 2 confirmed remission of her symptoms of depression at this time. Ms. G claims that she discovered its antidepressant effects accidentally after smoking the herb and had later developed a method of oral consumption which she claimed maintained its antidepressant effects even after she abstained from using it for up to a week”. Preliminary research (animal models) asserts Ms. G’s case and shows that Salvinorin A might become a therapeutic agent in the treatment of depression.

Carlezon et al. (2006) found that Salvinorin A “decreased extracellular concentrations of dopamine within the nucleus accumbens, a critical component of brain reward circuitry, without affecting extracellular concentrations of serotonin (5-HT)”. Butelman et al. (2004) showed that “the naturally occurring hallucinogen Salvinorin A produces discriminative stimulus effects similar to those of a high efficacy κ-agonist in non-human primates” (rhesus monkeys). Much research is done in the field of addiction and focuses primarily on Salvinorin A’s supposed anti-addictive effects. Activating the kappa-opioid receptors (KORs or KOPrs) produces anti-addictive effects by regulating dopamine levels in the brain (Kivel et al., 2014). The κ-opioid receptor may provide a natural addiction control mechanism, and therefore, drugs that act as agonists and increase activation of this receptor may have therapeutic potential in the treatment of addiction. “Activation of KORs”, says Tomasiewicz (2008), “reduces the reward-related effects of cocaine. Inasmuch as cocaine-induced behavioral stimulation in rodents may model key aspects of enhanced mood in humans, these findings raise the possibility that KOR agonists might ameliorate symptoms of conditions characterized by increased motivation and hyperfunction of brain reward systems, such as mania and stimulant intoxication”. These are obviously very exciting effects. “The development of KOPr-selective agents with improved drug-like characteristics” says Carlezon (2009), “would facilitate preclinical and clinical studies designed to evaluate the possibility that KOPrs are a feasible target for new medications”.

“Unfortunately”, says Kivel (2014), “classic kappa-opioid agonists have undesired side effects such as sedation, aversion, and depression, which restrict their clinical use”. Acute activation of kappa opioid receptors produces ‘anti-cocaine’ like effects, but because of considerate adverse effects their clinical use has remained limited (Simonson, 2014). Salvinorin seems to sidestep this problem. “Salvinorin A and its semi-synthetic analogs”, says Simonson (2014), “have been shown to have potent KOPr agonist activity and may induce a unique response with similar anti-cocaine addiction effects as the classic KOPr agonists but with a different side effect profile”. Salvinorin A retains the anti-addictive properties of traditional kappa-opioid receptor agonists with remarkable reduction of side effects.

However, there are still many obstacles to be overcome. For instance, a major problem is Salvinorin A’s rapid metabolism in the human body. Because of the short length of activation, Salvinorin as such will probably not be a good candidate for clinical development. In an effort to re-engineer Salvinorin’s pharmacokinetics, researchers have sought to produce kappa-opioid receptor agonists based on the structure of Salvinorin A that do have the desired length of activity. “While work in this field is still in progress”, says Kivel (2014), “several analogs with improved pharmacokinetic profiles have been shown to have anti-addictive effects”. These new analogs will eventually provide the characteristics sought after by clinical researchers for treatment.

Given the reemergence of interest into psychedelics and their potential as therapeutic agents it is hardly surprising that Salvia divinorum would attract attention. Salvia manifests a powerful psychedelic experience which is grounded in a unique neurochemical process which seems to have anti-addictive potential. It is surely a substance worth exploring within the psychiatric and psychopharmacological disciplines in the future.

 
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