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Psilocybin and Mood Regulation

December 6, 2021 / Articles, Mushrooms / Psilocybin, Publications, Research / By

With their recent publication, Kraehenmann et al. (2014) have increased our understanding of the mechanism that is thought to underlie the potential effectiveness of psychedelic–assisted psychotherapy in relieving mood and anxiety related symptomology. Their results elaborate on earlier findings that the administration of psychedelics [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 addition with psychotherapy reduces anxiety symptoms on a relatively short term (Gasser et al., 2014; Moreno, Wiegand, Taitano, & Delgado, 2006), with one study even showing a reduction of anxiety and an increase of positive mood six months after only a single dose of psilocybin (Grob et al., 2011).

These clinical observations are now complemented by the finding that psilocybin attenuates amygdala [2] reactivity in response to emotionally loaded pictures in healthy volunteers, and that these changes are associated with a positive mood change. The authors suggest that psilocybin might have the potential to normalize neurobiological systems that are dysregulated in individuals with a depressed mood state. In addition to the psychometric evidence and clinical observations that psilocybin-assisted psychotherapy improves mood within a clinical population, the results of the current study provide a possible neurobiological explanation for these effects. The questions that arise from this study relate to the degree to which these results can be generalized to a clinical population, and if and to what extent the acute changes in amygdala reactivity by themselves may account for long term changes in the processing of emotions.

According to the Trimbos Institute (2014) [3] there is a current prevalence of 4 – 10 % of people suffering from depression in Western society. Because of its high prevalence and devastating individual and societal consequences, depression is considered a major public health problem (Spijker, van Straten, Bockting, Meeuwissen, & van Balkom, 2013). The regular treatment options include psychotherapy, pharmacotherapy or a combination of the two, of which the latter is thought to establish the most favorable outcome. One of the added values of the study of Kraehenmann (2014) is the finding that psilocybin – with its pharmacological effect on amygdala reactivity – shares a neurobiological mechanism of action with selective serotonin reuptake inhibitors (SSRI’s), which are prescription drugs that are commonly deployed in the treatment of depression and other mood related disorders. What then, might be the necessity of exploring these psychedelic compounds as alternatives for customary treatment options?

The treatment of mood disorders with SSRI’s has several disadvantages, with probably the most prominent criticism being the modest response (47%) and remission rates (between 28 – 33%; Trivedi et al., 2006). Other disadvantages include a delayed therapeutic action (Stahl, 1998), withdrawal difficulties (Schatzberg, 1997), and the daily pharmacological treatment routine. Results from the psychedelic-assisted treatment sessions imply a prolonged uplift of mood after the pharmacological intervention, which is only implemented occasionally. These results are far too preliminary to abandon the extensively reviewed prescription drugs in the treatment of mood disorders and switch to less scientifically studied compounds that share some of the same neurobiological features, but it might be valuable to elucidate upon their therapeutical potential. What is it that psychologically distinguishes one type of drug with antidepressant properties from the other, and who are the people that might benefit from making this distinction? With one out of ten people suffering from depressive symptoms [4], the need for this kind of knowledge may not be underestimated.

 
[1] Red. classical psychedelics, which are isolated from a broader categorization of psychedelics by their pharmacological manifestation as serotonin 5-HT2A receptor agonists
[2] The amygdala is a structure in the limbic system that plays a major role in the processing of emotions and is therefore a key target for psychopharmacological interventions to treat mood and anxiety disorders (Phelps & LeDoux, 2005)
[3] The Trimbos Institute is a Dutch organization that serves as an information centre for matters related to mental health
[4] In Western societies (Trimbos Institute, 2014)
 
References
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, 00(00), 1. doi:10.1097/NMD.0000000000000113
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68(1), 71–8. doi:10.1001/archgenpsychiatry.2010.116
Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenweider, F. X. (2014). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological Psychiatry, 1–9. doi:10.1016/j.biopsych.2014.04.010
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder. The Journal of Clinical Psychiatry, 67(11), 1735–1740. doi:10.4088/JCP.v67n1110
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder. The Journal of Clinical Psychiatry, 67(11), 1735–1740. doi:10.4088/JCP.v67n1110
Spijker, J., van Straten, A., Bockting, C. L. H., Meeuwissen, J. a C., & van Balkom, A. J. L. M. (2013). Psychotherapy, antidepressants, and their combination for chronic major depressive disorder: a systematic review. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 58(7), 386–92. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23870720
Stahl, S. M. (1998). Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. Journal of Affective Disorders, 51(3), 215–35. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10333979
Trimbos Instituut (2014). Feiten en cijfers depressie. Reviewed on July 12, 2014 at http://www.trimbos.nl/onderwerpen/psychische-gezondheid/depressie/feiten-en-cijfers
Trivedi, M. H., Rush, a J., Wisniewski, S. R., Nierenberg, A. a, Warden, D., Ritz, L., … Fava, M. (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. The American Journal of Psychiatry, 163(1), 28–40. doi:10.1176/appi.ajp.163.1.28[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]

Autism and LSD-25 – Freeing the Most Imprisoned Minds?

February 7, 2022 / Articles, Background articles, LSD, Research / By

In the early sixties, a number of controversial clinical investigations were published involving the administration of LSD-25 (lysergic acid diethylamide) to young children said to suffer from severe forms of autism, or childhood-onset schizophrenia (COS), which were then regarded as closely related [1]. The reason for conducting the studies with young children was the supposed similarity between autism and COS. Prompted by the apparent results of studies conducted with LSD-25 and adult mute catatonic patients by Cholden, Kurland, and Savage (1955), hypotheses were constructed to research a possible therapeutic utility. “The goal in these therapeutic efforts”, said Bender in an article published in Recent Advances in Biological Psychiatry (1962), “has been to modify the secondary symptomatology associated with retarded, regressed, and disturbed behavior of the children”. The larger part of the children treated with LSD in these studies were between six and ten years old and completely unresponsive to all other forms of treatment. That the children couldn’t be treated by other means served, in part, for the justification for using a powerful psychoactive substance in child experiments. Surely this decision would have been criticized by the ethical commission today.

A pharmacological intervention by means of LSD was said to “nudge the lagging maturation” (Bender, 1962) into a (somewhat) normal developmental pattern. How exactly the administration of LSD would accomplish the “freeing of the most imprisoned minds” was still unknown (Mogar & Aldrich, 1969). LSD was supposed to achieve success through “breaking through the autistic defense” (Bender, 1963), and in this way be exceptionally helpful in “areas which are closely related to the process of psychotherapy” (Simmons et al., 1966). Some believed LSD was especially useful at helping patients to “unblock” repressed subconscious material through other psychotherapeutic methods (Cohen, 1959). Therapists took LSD to establish a connection with the experience of schizophrenia. “During the ‘model psychosis’ phase of LSD research when the psychedelic state was considered a chemically-induced schizophrenia”, says pioneer LSD researcher Stanislav Grof (1980), “LSD sessions were recommended as reversible journeys into the experiential world of psychotics which had a unique didactic significance”.

Some researchers, like Freedman et al. (1963), studied LSD for its supposed psychotomimetic (psychotogenic) properties, meaning that the drug mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to merely hallucinations (Sewell et al., 2009). An exacerbation of ‘typical’ symptoms meant an opportunity for studying the (child)schizophrenic condition. Other researchers (Bender et al., 1963; Rolo, et al., 1965) considered the neurological mechanism behind the effect of LSD, which in that time was still highly obscure, as more important than its role as facilitator of the therapeutic process. For instance, LSD attracted theoretical interest as a serotonin inhibitor and an autonomic nervous system stimulant. Bender et al. (1963) concluded that “LSD-25 given daily in oral doses of 100 mcg [2] to pre-puberty autistic schizophrenic children appears to be an effective autonomic and central nervous system stimulant”, and that these changes “appear to be chronic with continuous administration of the drug”. Continuous administration consisted of daily administration over prolonged periods of time, varying from days to several weeks . The most persistent effects of LSD-25 therapy that were published included improved speech behavior, increased emotional responsiveness, positive mood (laughter) and a decrease of compulsions.

But alas, however interesting and attractive these results seemed to be — the evidence didn’t stick. Today studies into the relationship of LSD and autism aren’t being conducted and the results that were produced are regarded as highly controversial, if not completely repudiated. This was in part because, in retrospect, the studies were greatly flawed. The researchers seemed to have brushed over the conceptual controversy too quickly by choosing “not to deal with the controversial issues concerning the definitions and etiological factors of either childhood schizophrenia (1) or the autistic reaction pattern (2)” (Bender et al., 1962). The debate about the correct place of (childhood) autism within the DSM (Diagnostic and Statistical Manual of Mental Disorders) remains problematic to this day (DSM-V), but autism has long been divorced from the umbrella of schizophrenia. Although both disorders share clinical features, clinical psychologists and psychiatrists regard autism to be a separate diagnostic ‘entity’ from schizophrenia. Because LSD was used as a drug for “intensifying pre-existing symptomology” of schizophrenia (Bender et al., 1962), a conceptual detachment from autism would have disturbed the foundation of the results.

Even if the researchers had chosen to ‘deal with the controversy’, in hindsight, sampling would have still ended up being very problematic. The children treated were demographically varied and covered a broad age range. Conflicting significance is given to the relationship between age and drug response, but Bender noted that “in contrast to pre- adolescents, younger children manifest consistently different reactions” (1962). In contrast, Fisher and Castile concluded that “older children were better candidates for psychedelic therapy because verbal communication was possible and also because they tended to be less withdrawn, more schizophrenic than autistic, and displayed more blatant symptomology” (Mogar & Aldrich, 1969). In addition to age, also the symptoms of treated children were heterogeneous and weren’t corrected for severity. There was no randomization, and most studies suffered from fluctuating frequency of administration and dosage. Lastly, the set and setting of the experiments varied strongly.

Although the studies conducted in the sixties had major flaws from an experimental point of view and therefore didn’t hold up to scientific scrutiny, Mogar and Aldrich argue in an article published in Behavioral Neuropsychiatry (1969) that the results considered as a whole do point to a utility of administering LSD to autistic children. “The significance of seemingly contradictory results”, say Mogar and Aldrich, “has often been obscured by the persistent search for static, ‘drug-specific’ reactions to LSD”. This is an interesting point; despite that the results don’t indicate significance in an experimental sense, there may still be a therapeutic utility. Mogar and Aldrich report that the greatest therapeutic benefit was related to “(a) the degree of active therapist involvement with the patient; (b) an opportunity to experience meaningful objects and interpersonal activities; and (c) congenial settings that were reasonably free of artificiality, experimental or medical restrictions, and mechanically administered procedures” (1969). In practice clinical therapy is usually far removed from theory. It could be that testing LSD, itself being a highly unpredictable drug, in combination with the therapy dynamic is too hard to substantiate. Mogar and Aldrich conclude that “the administration of LSD is inextricably embedded in a larger psychosocial process which should be optimized in accordance with particular treatment goals”.

Considering the recent growth of interest into this area of research, these older and rather obscure studies deserve to be excavated from the psychedelic research literature. Researchers at LA BioMed (Los Angeles Biomedical Research Institute) are now constructing a study which is said to test the already established anecdotal therapeutic relationship between MDMA (3,4-methylenedioxy-N-methylamphetamine) and autism in adults. The study is the latest in an expanding program of research into the therapeutic use of MDMA funded by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS). “This new study will give us a chance”, says Charles Grob head researcher at LA BioMed (2014), “to determine the actual effects of differing dosages of medication that we know for certain is pure MDMA on adults on the autism spectrum. If the results of this research warrant further investigation, data from this study will be used to design additional clinical trials”. Now that the limitations for research into the psychedelic experience and its therapeutic effects are being removed and LSD is once again an object of study, these previously published results could serve for the production of new hypotheses.

 
[1] See (Abramson, 1960; Bender, et al., 1962; Bender, et al., 1963; Fisher & Castile, 1963; Freedman, et al., 1962; Rolo, et al., 1965; Simmons, et al., 1966).
[2] A common psychedelic dosage of LSD ranges from 100 to 200 mcg, a strong dose being 200 to 600 mcg.
 
References
Abramson, H.A. (Ed.) (1960). The Use of LSD in Psychotherapy. New York: Josiah Macy Foundation.
Bender, L., Faretra, G., & Cobrinik, L. (1963). LSD and UM-L treatment of hospitalized disturbed children. Recent Advances in Biological Psychiatry, 5, 84-92.
Bender, L., Goldschmidt, L., & Sankar, S.D.V. (1962). Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Advances in Biological Psychiatry, 4, 170-177.
Cholden, L., Kurland, A., & Savage, C. (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous and Mental Disease, 122, 211-216.
Cohen, S., & Eisner, B. G. (1959). Use of lysergic acid diethylamide in a psychotherapeutic setting. AMA Archives of Neurology & Psychiatry, 81(5), 615-619.
Freedman, A.M., Ebin, E.V., & Wilson, E.A. (1962). Autistic schizophrenic children: An experiment in the use of d-lysergic acid diethylamide (LSD-25). Archives of General Psychiatry, 6, 203-213.
Gettys, T. (2014). MDMA Helps Reduce Social Anxiety for Autistic Adults, and Researchers Want to Find Out How. MAPS. Retrieved at: http://www.maps.org/media/view/mdma_helps_reduce_social_anxiety_for_autistic_adults_and_researchers_w/
Grof, S. (1980). LSD Psychotherapy. California: Hunter House Publishers.
Mogar, E. R., & Aldrich, W. R. (1969). The Use of Psychedelic Agents with Autistic Schizophrenic Children. Behavioral Neuropsychiatry, 1(8), 44-50.
Rolo, A., Krinsky. L.W., Abramson, H.A., & Goldfarb, L. (1965). Preliminary method for study of LSD with children. International Journal of Neuropsychiatry, 1, 552-555.
Sewell, R. A., Ranganathan, M., & D’Souza, D. C. (2009). Cannabinoids and psychosis. International Review of Psychiatry, 21(2), 152-162.
Simmons, J.Q., Leiken, SoJ., Lovaas, Q.I., Schaffer, B., & Perloff, B. (1966). Modification of autistic behavior with LSD-25. The American Journal of Psychiatry, 122, 1201-1211.

Survey: Ayahuasca Consumption in Europe

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

survey_508

Researchers are calling for participants to complete an anonymous online questionnaire about their ayahuasca consumption. This information will be presented at the upcoming World Ayahuasca Conference in September 2014.

The researchers are looking for people living in Europe who have already used ayahuasca, including those who no longer partake. The aim of the questionnaire is to create a comprehensive profile of European ayahuasca users and better understand their motivation for drinking ayahuasca, as well as how it may have benefited them.

To take the survey, click here. The survey takes 15 minutes and is completely anonymous.

Ketamine Reconsidered

February 7, 2022 / Articles, Background articles, Ketamine, Research / By

Ketamine is causing a lot of ‘buzz’ inside neuropsychiatry at the moment. Duman and Aghajanian called the substance in Science (2012) “the biggest breakthrough in depression research in a half century”. The APA (American Psychiatric Association) is dedicating a surprisingly large amount of time discussing the new implications concerning ketamine in the 167th ‘annual meeting’ this year (2014). Abrams says in The Atlantic (2012) that the effects of ketamine suggest that depression isn’t caused by a chemical imbalance in the brain, as is believed by most neuropsychologist, but by damage to brain cells caused by chronic stress. Ketamine is said to stimulate the process of synaptogenesis (the formation of synapses in the brain), which repairs the damage caused by stress (Zarate 2006, Duman 2012). These findings could eventually become the base for a “synaptogenic hypothesis” of depression (Duman, 2012).

Ketamine is used very diversely in scientific studies [1], which shows well how contingent the ideas surrounding a substance can be. In 1962, eight years before the American president Nixon signed the Controlled Substances Act and shut the door for research of the effects of substances like LSD, psilocybin and mescaline, ketamine was synthesised in the Parke Davis Lab in Detroit. Ketamine is considered an arylcyclohexylamine in chemistry, the same category that phencyclidine (PCP) belongs to. Ketamine, then still CI581, was initially explained as a fast-acting anesthetic for general use. It was used in the instance of severe damage to the skin caused by radiation or burns. Children were given ketamine when they had bad reactions to other tranquilizing substances or when a more superficial anesthesia was called for. Ketamine’s effects were popular in animal medicine as well. In 1970 ketamine started playing a significant role in the Vietnam war. Upon return, many veterans told stories about odd mental experiences which they had during operations for their injuries. It’s only when ketamine started to be used recreationaly [2] that the dissociative effect, the literal separation of mind and body, came to the forefront.

In 1973, near the end of the Vietnam war, the Iranian psychiatrist E. Khorramzadeh published an article on the use of ketamine during psychotherapy in Psychosomatic Journal. In South-America, this led to the emergence of several therapies which used ketamine as a means for psychoanalytical regression. John C. Lilly published his phenomenological magnus opus The Scientist in 1978, which made his own experiments as well as that of others in the field available for philosophical scrutiny. Lilly came to the conclusion that ketamine opens the door for ‘metaprogramming’ [3], a process which he describes as the conscious manipulation of the synapses to cause changes in behavior and personality patterns. In that same year Journeys into the Bright World by Marcia Moore and her husband Howard Alltounian appeared, which explored the possibility of using ketamine in Jungian psychotherapy. Krupitsky brought ketamine together with addiction therapy in 1985. Krupitsky, head of the research laboratory for addiction and psychopharmacology in St. Petersburg, developed a ‘psychedelic therapy’ which, to his own surprise, resulted in complete abstinence of at least a year in 66% of his alcohol addicted patients (1995). In collaboration with Strassman, famous for his monumental study into DMT and the book The Spirit Molecule (2000) which followed it, Krupitsky published the results of a study into ketamine and heroin addiction. Although ketamine did not show lasting effects of abstinence, which the researchers sought, there was a noticeable improvement in the withdrawal process. They accredited these results to a positive transformation of the self-concept as well as in emotional, moral and spiritual attitudes.

Karl Jansen, eminent ketamine researcher and proponent of further psychotherapeutic integration of the experiences induced by ketamine, adds an important layer to the work of Krupitsky. He proposes that the experience which ketamine offers is therapeutic in itself. Jansen draws a comparison between ketamine and the state of consciousness that people experience ‘near death’. According to Jansen this experience, like with ketamine, has effects on personality; it increases altruistic behavior, decreases the fear of death and makes people less materialistic (2001).

Modern neuroscientist go a step further than Krupitsky; that ketamine is itself effectively therapeutic, according to them has got little to do with the psychedelic experience. The experience as therapeutic process is replaced with a neurochemical mechanism. The characteristics of the experience or the impressions which people extract out of it don’t account for the therapeutic effect, according to these neuroscientists the therapeutic effect is caused by an intervention outside of consciousness. The qualities which are desired in the eyes of psychonauts [4] are annoying side-effects which they have to get rid of to be able to use ketamine as an antidepressant. According to researchers of other psychedelic substances ketamine’s growing success is a good opportunity to get attention for their results. However, it remains to be seen if this doesn’t devalue research into the psychedelic experience.

The effects that ketamine appears to have on the mental condition of individuals with a depression diagnosis were introduced by researchers like John Krystal and Karl Jansen, but until Zarate et al. (2006) there weren’t any robust double-blind placebo controlled studies conducted. Zarate et al. found a strong and fast antidepressant effect with a single dose of ketamine. Unfortunately the amount of time that the effects lasted still varied too much, from two days to two weeks. They concluded that ketamine, at the present moment, should at least play a role in acute suicidal episodes. It’s still unknown if or how the antidepressant effect can be lengthened. Baumeister et al. conducted a meta-analysis, published in Therapeutic Advances in Psychopharmacology (2014), in which they present evidence for the effects of ketamine in the treatment of depression, even when study samples were still relatively small. In any case, the results support the further exploration of administering ketamine to individuals with a severe and therapy resistant depression diagnosis. Ruud Kortekaas, a Dutch neuroscientist at the UMCG (Universitair Medisch Centrum Groningen), is now conducting a study into the long term effects (twenty weeks) of ketamine administration to people who don’t react [5] to regular antidepressants. Kortekaas attributes the effects of ketamine in his patients to a heightened activity in the prefrontal lobe. “It’s like all of those rusty taps in the brain”, says Kortekaas in the Volkskrant (Mudde, 2012), “are completely opened in one go. Often patients experience a strong improvement within several hours. Substances like Prozac, if they work, only start having effects after weeks. Here there is an immediate effect which lasts for days, in small pilot studies in eight out of ten patients”. Ketamine stimulates, in rather low dosages, the process of synaptogenesis which increases the plasticity of the brain (Zarate 2006, Duman 2012). Rasmussen et al. published in Journal of Psychopharmacology (2013) that a low dose of ketamine intravenously is effective in alleviating depressive symptoms in half of their subjects. Rupert McShane, researcher at Oxford Health NHS Foundation Trust, even rapports an effect of several months in a small study published in Journal of Psychopharmacology (2012). In Kortekaas’s study the focus will be on examining the different nuances of different dosages. The study is unique because an oral form of administering ketamine was choses while most other studies based their results on intravenous, intramuscular or nasal forms. An oral form will, according to Kortekaas, result in a strong growth of ketamine’s applicability as antidepressant. Also, the low dosages which are used in the study are hardly psychoactive, and therefore will almost have no influence on normal functioning. The study is set up as a randomized controlled trial (RCT) with 100 participants (50 placebo) in which individuals will receive a functional magnetic resonance imaging scan (fMRI) before ketamine administration and after completing three weeks. “If this study is successful”, says Kortekaas, “it would mean the first step in getting a large amount of people, which don’t react to conventional substances, back into society”. “It’s exciting”, says psychiatrist and neurobiologist Duman (2012), “the hope is that this new information about ketamine is really going to provide a whole array of new targets that can be developed that ultimately provide a much better way of treating depression”.

There aren’t a lot of substances which had its utility reconsidered as often as ketamine. Moreover, the different paradigms surrounding ketamine aren’t mutually exclusive. It’s possible that the same substance could be regarded as an antidepressant in low dosages, a psychedelic in higher dosages and in the highest dosage range a total anesthetic. The nuances between these states must be carefully examined in the future, certainly when ketamine will become available to greater amounts of people as an antidepressant.

 
[1] Ketamine as a model for schizophrenia (Fletcher et al., 2006), ‘body ownership’ (Fletcher et al., 2011), analgesic (Menigaux et al., 2001), ‘sense of agency’ (Moore et al., 2013), perception of time (Coul et al., 2011), morphine synergism (Schulte et al., 2004).
[2] Recreational use of ketamine was first documented in the beginning of the 70s in the underground publication The Fabulous Furry Freak Brothers.
[3] He borrowed this term from computer science where metaprogramming is the writing of a computer program which itself is able to write or manipulate programs.
[4] Psychonautics refer to the paradigm in which the phenomenology of psychoactive substances is examined.
[5] Individuals that don’t react to SSRI’s (selective serotonin reuptake inhibitors) and TCA’s (tricyclic antidepressant).
 
References
Abrams, L. (2012). The Biggest Breakthrough in Depression Research in 50 years is… Ketamine? The Atlantic. Retrieved at: http://www.theatlantic.com/health/archive/2012/10/the-biggest-breakthrough-in-depression-research-in-50-years-is-ketamine/263400/
American Psychiatric Association. (2014). APA 167th annual meeting proceedings. Washington, DC: Author. Retrieved at: http://psychnews.psychiatryonline.org/newsarticle.aspx?articleid=1816463
Baumeister, D., Barnes, G., Giaroli, G., & Tracy, D. (2014). Classical hallucinogens as antidepressants? A review of pharmacodynamics and putative clinical roles. Therapeutic Advances in Psychopharmacology, 2045125314527985.
Coull, J. T., Morgan, H., Cambridge, V. C., Moore, J. W., Giorlando, F., Adapa, R., Corlett, P. R., Fletcher, P. C. (2011). Ketamine perturbs perception of the flow of time in healthy volunteers. Psychopharmacology (Berl) 218(3):543-56.
Diamond, P. R., Farmery, A. D., Atkinson, S., Haldar, J., Williams, N., Cowen, P. J., … & McShane, R. (2014). Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic. Journal of Psychopharmacology, 0269881114527361.
Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: potential therapeutic targets. Science, 338(6103), 68-72.
Fletcher, P. C., Honey, G. D. (2006), Schizophrenia, ketamine and cannabis: evidence of overlapping memory deficits. Trends in the Cognitive Sciences 10(4):167-174.
Jansen, K. (2001). Ketamine: Dreams and Realities. MAPS (Multidisciplinary Association for Psychedelic Studies).
Khorramzadeh, E., & Lotfy, A. O. (1973). The use of ketamine in psychiatry. Psychosomatics, 14(6), 344-346.
Krupitsky E., Burakov, A., Romanova, T., Dunaevsky, I., Strassman, R., Grinenko A. (2002). Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment, 23, 273-283.
Krupitsky, E. M. (1995). Ketamine psychedelic therapy (KPT) of alcoholism and neurosis. In: Yearbook of the European College for the Study of Consciousness (Leuner, H., ed.), pp.113-121. Berlin: Verlag Fur Wissenschaft und Bildung.
Lilly, C. J. (1978). The Scientist: A Novel Autobiography (1st ed.). Philadelphia: Lippincott.
Moore, M., & Alltounian, H. (1978). Journeys into the Bright World. Gloucester: Para Research Inc.
Moore, J. W., Dickinson, A., Fletcher, P. C. (2011). Sense of agency, associative learning, and schizotypy. Conscious Cogn 20(3):792-800.
Moore, J. W., Cambridge, V. C., Morgan, H., Giorlando, F., Adapa, R., Fletcher, P. C. (2013). Time, action and psychosis: using subjective time to investigate the effects of ketamine on sense of agency. Neuropsychologia 51(2):377-84.
Morgan, H. L., Turner, D. C., Corlett, P. R., Absalom, A. R., Adapa, R., Arana, F. S., Pigott, J., Gardner, J., Everitt, J., Haggard, P., Fletcher, P. C. (2011). Exploring the impact of ketamine on the experience of illusory body ownership. Biol Psychiatry 69(1):35-41.
Mudde, T. (2012). Trippen voor de Wetenschap. Volkskrant. Retrieved at: http://www.volkskrant.nl/vk/nl/2844/Archief/archief/article/detail/3327458/2012/10/06/Trippen-voor-de-wetenschap.dhtml
Rasmussen, K. G., Lineberry, T. W., Galardy, C. W., Kung, S., Lapid, M. I., Palmer, B. A. & Frye, M. A. (2013). Serial infusions of low-dose ketamine for major depression. Journal of Psychopharmacology, 2

Psychedelic Resurgence

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

This year’s first edition of The Journal of Psychoactive Drugs is a special issue dedicated to the resurgence of psychedelic research. In roughly five themes (LSD, MDMA , ayahuasca, cannabis, research issues and institutes) the journal provides a glance at past and present matters related to research and therapeutic uses of psychedelics.

The first article is a review of the past, present and future status of Lysergic Acid Diethylamide (LSD; Smith, Raswyck, & Dickerson Davidson, 2014). The article comprises a chronological overview of how the psychoactive properties of LSD have led to positive and negative appraisal of the substance in therapeutic research, for military purposes, and recreational use. The article finishes with an overview of contemporary research projects. Another LSD-centered article in the journal, is a qualitative study that retrospectively assesses the long-term experiences of Czech psychologists and psychiatrists that involved in self-experimentation with LSD in the 1950’s – 1970’s (Winkler & Csémy, 2014). The article also serves to present arguments for self-experimentation.

Two review papers are dedicated to address the pro’s and con’s of using MDMA in a therapeutic setting and research issues related to the “Ecstacy Paradigm” (Cole, 2014; Parrott, 2014). A consideration of how psychiatry and psychedelics can benefit from each other, is provided by dr. Ben Sessa (2014), who has been working on MDMA-assisted psychotherapy.

In a qualitative study, Loizaga-Velder and Verres (2014) explored the therapeutic effects of ritual ayahuasca use in the treatment of substance abuse. In line with other studies that yielded promising results in exploring the competence of psychedelics in treating addiction (Heffter Institute, 2012; Krupitsky et al., 2007), the main finding was that participation in ritual ayahuasca sessions facilitated substance dependence treatment.

In New-Mexico, the first state that authorized the use of medicinal cannabis for releasing symptoms of Post-Traumatic Stress Disorder (PTSD), Greer, Grob, and Halberstadt (2014) acquired retrospective data in order to portray the result of this law adjustment. The researchers tentatively conclude that cannabis is associated with PTSD reduction in some patients, and express the need for a study with an experimental design.

An inspiring contribution to this special issue, are two articles dedicated to the past and present of the Heffter Research Institute and the Multidisciplinary Association for Psychedelic Studies (MAPS; Emerson, Ponté, Jerome, & Doblin, 2014; Nichols, 2014). As the editor of the journal, Terry Chambers, expresses in the introduction: ‘…this issue of the Journal is not a comprehensive presentation of the activity of those attempting to understand the properties and uses of psychedelic drugs, but it is an indication of the serious and interesting research being done on this subject.’ The resurgence is happening, and we expect that Dutch scientists will follow soon.

The journal is published online and the abstracts can be freely retrieved from our website.

 
References
Cole, J. C. (2014). MDMA and the “Ecstasy Paradigm.” Journal of Psychoactive Drugs, 46(1), 44–56. doi:10.1080/02791072.2014.878148
Emerson, A., Ponté, L., Jerome, L., & Doblin, R. (2014). History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS). Journal of Psychoactive Drugs, 46(1), 27–36. doi:10.1080/02791072.2014.877321
Greer, G. R., Grob, C. S., & Halberstadt, A. L. (2014). PTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program. Journal of Psychoactive Drugs, 46(1), 73–77. doi:10.1080/02791072.2013.873843
Heffter Research Institute. 2012. Our Research. Available at: http://www. heffter.org/research-hucla.htm.
Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V, Romanova, T. N., Slavina, T. Y., & Grinenko, A. Y. (2007). Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence. Journal of Psychoactive Drugs, 39, 13–19. doi:10.1080/02791072.2007.10399860
Loizaga-Velder, A., & Verres, R. (2014). Therapeutic Effects of Ritual Ayahuasca Use in the Treatment of Substance Dependence—Qualitative Results. Journal of Psychoactive Drugs, 46(1), 63–72. doi:10.1080/02791072.2013.873157
Nichols, D. E. (2014). The Heffter Research Institute: Past and Hopeful Future. Journal of Psychoactive Drugs, 46(1), 20–26. doi:10.1080/02791072.2014.873688
Parrott, A. C. (2014). The Potential Dangers of Using MDMA for Psychotherapy. Journal of Psychoactive Drugs, 46(1), 37–43. doi:10.1080/02791072.2014.873690
Sessa, B. (2014). Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry. Journal of Psychoactive Drugs, 46(1), 57–62. doi:10.1080/02791072.2014.877322
Smith, D. E., Raswyck, G. E., & Dickerson Davidson, L. (2014). From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide. Journal of Psychoactive Drugs, 46(1), 3–10. doi:10.1080/02791072.2014.873684
Winkler, P., & Csémy, L. (2014). Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia. Journal of Psychoactive Drugs, 46(1), 11–19. doi:10.1080/02791072.2013.873158

Hofmann’s Wish Came True

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

After 40 years without research, the recent appearance of a pilot study with Lysergic Acid Diethylamide (LSD) in humans, might be interpreted as a positive reinforcement for future attempts to study the role of psychedelics as therapeutic agents. The study of Gasser et al. (2014) was aimed at assaying the possible benefits from the use of LSD as an additive to psychotherapy in the treatment of anxiety associated with life-threatening diseases.

The participants in the double blind, randomized, active placebo-controlled study were recruited from a population of patients diagnosed with a life-threatening disease. The participants were randomized across two-groups and received two therapeutic sessions with LSD (mild-dose placebo-control group; moderate-dose experimental group) in addition to psychotherapy. The patients that were initially assigned to the placebo-control group, were offered the opportunity to participate in a second series of moderate-dose LSD-assisted therapies (open-label crossover group). The most important result from the study was that with each cumulative LSD session, anxiety seemed to reduce in the group that received a moderate dose, but not in the group that received a mild dose. In the latter group, this pattern of reduced anxiety was repeated with the second series of sessions in which the moderate dose was offered to the patients. The benefits of the LSD-assisted sessions seemed to sustain over time. Though methodological adjustments are preferred to improve matters of experimental reliability and validity (as the authors note a larger sample size, a less discriminative placebo, better treatment of secondary disease symptoms to avoid missing data), the reactions of the patients themselves suggest successful clinical guidance during the process of coping with death. Majority reported that they would have preferred more than two LSD sessions and a longer treatment period.

Not only did the study yield promising results about the controversial use of a Schedule 1 listed drug (21 U.S.C. § 812) in a therapeutic setting, the publication also received extensive international media attention (Carey, 2014; Healey, 2014; Connor, 2014) suggesting a regained public interest favoring psychedelic research. While directly after discovery the psychoactive effects of LSD were considered to be of considerable value for experimental research and psychiatric practice (Passie, Halpern, Stichtenoth, Emrich, & Hintzen, 2008), it’s reputation of the past 40 years was mainly that of a dangerous drug (SAMHSHA, 2008). In addition to a recent clinical study done with psilocybin (Grob et al., 2011) , the current study contributes to a refreshed wave that acknowledges the usefulness of psychedelics as an investigational tool for psychiatric research. With the resumption of research into LSD’s therapeutic potential, the researchers hope to have “fulfilled the longtime wish” of the founding father of LSD, Albert Hofmann, as to whom the article is dedicated.

 
References
Carey, B. (2014, March 4). LSD, Reconsidered for Therapy. The New York Times. Retrieved from http://www.nytimes.com
Connor, S. (2014, March 6). Can LSD ease our fear of death? First scientific study in 40 years shows positive results. The independent. Retrieved from http://www.independent.co.uk
Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., Brenneisen, R. (in press). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68, 71–78. doi:10.1001/archgenpsychiatry.2010.116
Healy, M. (2014, March 5). First trial of LSD as medicine in 40 years shows promise. The Los Angeles Times. Retrieved from http://www.latimes.com
Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The pharmacology of lysergic acid diethylamide: a review. CNS Neuroscience & Therapeutics, 14, 295–314. doi:10.1111/j.1755-5949.2008.00059.x
SAMHSA. Available at http://www.oas.samhsa.gov/ecstasy.htm, 2006. Accessed on 08 March 2014.
U.S. Food and Drug Administration. (2009, June 6). Controlled Substance Act. Retrieved from http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm

New study may explain magic mushrooms' effects

February 7, 2022 / Articles, Background articles, Mushrooms / Psilocybin, Research / By

New research by a group of mainly Britisch scientists, based on fMRI brain scans, has shown that the use of psilocybin (the active constituent of magic mushrooms) decreases the activity of certain parts of the brain in test subjects. Brain activity decreased especially in those parts that are involved in the managing and filtering of information.

This may explain why users often report that under the influence of magic mushrooms they experience impressions and feelings that were previously unnoticed. Logically, when the brain’s ability to filter and handle information is decreased, more information may reach our consciousness. This may also explain why users often report new insights after the use of magic mushrooms, sometimes having therapeutic effects.

Another indication for the therapeutic effects of magic mushrooms is that brain activity also decreased in the medial prefrontal cortex, a brain part that is often hyperactive in patients suffering from depression.

Remarkably, these new results confirm the ideas of Aldous Huxley (1894-1963). Huxley saw the brain as a ‘reducing valve’, filtering and making information more manageable for our consciousness. He posed that psychedelic drugs might decrease these reducing properties of the brain.

Click here for the abstract and a link to the full article.

Help pay for MDMA PTSD research

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

Recently, MAPS officially launched an Indiegogo campaign to help complete their crucial study of MDMA-assisted psychotherapy for people suffering from post-traumatic stress disorder (PTSD). OPEN supports MAPS in their efforts to raise both funds and awareness. Money is needed to progress vital research on these substances, while increasing awareness on the human and economic costs of PTSD can show that viable alternatives exist that can transform the lives of PTSD-sufferers.

The first published studies have shown that MDMA-assisted psychotherapy can be an effective treatment for people who did not respond to conventional therapies for post-traumatic stress disorder. MAPS’ studies are supported by the US government; their ongoing study in military veterans, firefighters, and police officers is halfway complete, and early results are promising. For some recent articles on MDMA-assisted PTSD-treatment, see here, here and here.

Donations will help pay the costs of conducting our ongoing clinical trial, a critical part of our international research program to develop MDMA-assisted psychotherapy into a prescription treatment for PTSD. Visit the Indiegogo page here,

A video-interview with one of the first subjects can be watched here:

Survey: New Drugs for Mental Health

December 6, 2021 / Articles, New substances, Publications, Research / By

After the recent published study on psychedelic substances and mental health, researchers are looking to explore this relation more deeply. The main aim of the survey is to gain novel insight towards un-noted benefits (and harms) of recreationally used drugs on mental health.

This survey was created by Imperial college, Prof D. Nutt, Dr R. Carhart-Harris and their team. According to the researchers, little is yet known about the effects on mental health of people who experiment with psychedelic substances. They are asking questions to gather information about potential usefulness for mental health of these new drugs and also to discover whether they have any unrecognised negative effects. Please click this link to participate in this recently launched online survey regarding psychoactive drugs and mental health.

Participants can fill in a different survey for each drug they want to say something about. Please only complete a survey if you have personal experience with a particular drug.

Responses will be treated as clinical information and are protected by medical confidentiality law. Your personal details will not be requested or stored.

Crowdfunding: Ayahuasca Treatment Outcome Project

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

An international scientific team – consisting of clinical psychiatrists and neuroscientists, medical doctors and anthropologists, epidemiologists and curanderos – is trying to set up an ambitious research project to study the effects of ayahuasca and how it affects addiction and other mental health issues. They have only 12 days left to reach their first funding goal of C$25.000, so please consider making a donation.

Since it can be a big challenge indeed to receive funding through traditional channels, OPEN supports funding serious research via other means. Donating means you are funding an interdisciplinary research design meeting contemporary high quality scientific standards, which involves thorough follow-up and a longitudinal assessment of treatment efficacy.

The team is being led by Dr. Brian Rush, Professor, Dept. of Psychiatry, University of Toronto, Canada and Scientist Emeritus at the Centre for Addiction and Mental Health, Toronto, Canada.

For more information and a video about this project have a look at their Indiegogo page.

22 May - Delivering Effective Psychedelic Clinical Trials

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