It is only a rough initial gathering of information and I welcome contributions of articles of interest and relevance and any feedback and discussion in the comments.

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

“Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.”

Robin L Carhart-Harris & Guy M Goodwin (2017)

Depression

Psilocybin and Depression

The Beckley Foundation discovered “that psilocybin may effectively ‘reset’ the activity of key brain circuits known to play a role in depression. There may also be a link between peak experience and the post treatment increase in connectivity between certain brain regions. So, peak experience could lead to the increases in connectivity after the experience, which in turn could lead to better therapeutic outcome.

Patients were also shown pictures of faces with various emotional content (fearful, neutral, happy) while in the scanner.  The analysis of brain images focused on the amygdala, a brain region involved in processing fear and stress. Activity in this brain region was stronger in response to being shown fearful faces after the psilocybin session than it was in response to those fearful faces beforehand. This means that psilocybin actually enhances the response to negative emotional stimuli. This might sound surprising – we’d imagine that successful antidepressant medication would reduce or dampen such activity. But the team actually found that the strength of this increased response was correlated with greater improvement. This implies that psilocybin-assisted therapy treats depression by enhancing emotional responsiveness.

The researchers make some fascinating observations from the interviews that were conducted with the patients in this trial, that help explain these findings. Many of these patients said that they attributed the effectiveness of the treatment to “a greater willingness to accept all emotions”. Many went so far as to say that they felt previous depression treatments had worked to “reinforce emotional avoidance and disconnection”. The psilocybin experience itself, by contrast, had precipitated an emotional “confrontation”: a challenging return to old traumas that had led to “emotional breakthrough and resolution”. The therapeutic process that was by no means easy or pleasant was nevertheless felt to have been pivotal to achieving a therapeutic transformation. These patient perspectives are supported by previous research demonstrating that the difficulty of a psychedelic therapy experience is in fact predictive of a better long-term result. Another apparently paradoxical finding, but one which echoes the approach of much traditional talking therapy.”

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study summary

Background

Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression.

Methods

In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptomswere assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797.

Findings

Psilocybin's acute psychedelic effects typically became detectable 30–60 min after dosing, peaked 2–3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0–1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1 week (mean QIDS difference −11·8, 95% CI −9·15 to −14·35, p=0·002, Hedges' g=3·1) and 3 months (−9·2, 95% CI −5·69 to −12·71, p=0·003, Hedges' g=2) after high-dose treatment. Marked and sustained improvements in anxiety and anhedonia were also noted.

Interpretation

This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials, with more rigorous designs, to better examine the therapeutic potential of this approach.

“New treatments for the substantial proportion (perhaps 20%) of patients with depression who do not recover well with either cognitive psychotherapy or medication are certainly needed. Unfortunately, the development of new, more effective medicines through the usual industry-led process of drug discovery has stalled. Intriguingly, into this void have come some repurposed older drugs, for example ketamine, scopolamine, and nitrous oxide by contrast with conventional antidepressants, these drugs produce rapid and profound changes in mood and consciousness. Ketamine has been the most studied and, although rapid alleviation of mood is reported in a reasonable proportion of patients, the effects are relatively transient and disappear after a few days as the pharmacological effect wanes. The concept underlying the use of psychedelic agents such as psilocybin seems quite different, namely that administration of one or two doses results in profound, spiritually meaningful experiences that produce enduring gains in wellbeing and personal adjustment.7 Such effects have not been studied systematically in patients with depression previously, but benefits have been claimed following the use of psilocybin to treat anxiety and distress during end-of-life care, and in patients with alcohol and nicotine dependence”

Phil Cowen, Department of Psychiatry, University of Oxford, in his article Altered states: psilocybin for treatment-resistant depression www.thelancet.com/psychiatry Vol 3 July 2016 Published Online May 17, 2016 http://dx.doi.org/10.1016/S2215-0366(16)30087-6

Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

“ABSTRACT=Introduction: It is a basic principle of the ‘psychedelic’ treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would not.

Material and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10mg and 25mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-time and DED-by-time interactions were the primary outcomes of interest.

Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson’s correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05).

Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. More specifically, future therapeutic work with psychedelics may consider investigating ways which enhance mystical-type experience and reduce anxiety, given the growing evidence that this serves the efficacy of the treatment model.”

Roseman Leor, Nutt David J., Carhart-Harris Robin L. (2018)

LSD and Depression

LSD was administered to cancer patients in the 1970 Pahnke et al study and saw a decrease in depression and anxiety in those patients.

“CNS deficiency of 5-hydroxytryplamine (serotonin) has been implicated as a biochemical basis in some forms of depression. Existing drug modalities for treating depression include some with serotonergic effects. Studies suggest that psychedelic drugs are also serotonergic, This may indicate a role for psychedelics in the treatment of depression. Such treatment has already been attempted using psychedelic drugs in both the indoleamine and phenylalkylamine categories. Encouraging results seem to recommend further research, with special emphasis on drugs in the phenylisopropylamine subgroup of phenylalkylamines that are only peripherally psychedelic. Certain of these, called entactogens or empathogens, cause substantially less distortion of normative consciousness than classic psychedelics, such as LSD or mescaline. They could therefore be more easily assimilated into existing psychotherapy approaches, where their function would be to enhance the normal psychotherapeutic process rather than serving a maintenance role as chemoth erapeutic agents. Their usefulness in such an application would be mainly at the start of psychotherapy in order to (1) reduce the client's “fear response” that often inhibits ability to deal with repressed traumatic material; (2) facilitate the client's interpersonal communications with the therapist, spouse or significant others; and (3) accelerate formation of a therapeutic alliance between client and therapist.” Thomas J. Riedlinger & June E. Riedlinger (1994) 

LSD: Therapeutic Effects of the Psychedelic Experience

“Preliminary results of a study of psychedelic therapy are reported. Patients receive LSD and mescaline in a supportive setting following intensive preparation. Subjective questionnaire data from 113 patients reveal a high frequency of claimed benefit, low frequency of negative reaction, and a high relation between claimed benefit and reported “greater awareness of ultimate reality” through the LSD experience. Clinical data on 74 cases including blind ratings of MMPI profiles substantiate the claimed improvement rate. Cases in each of five improvement categories are summarized and before, 2-mo.-after, and 6-mo.-after MMPI data are included. Total improvement rate is above 80%. Follow-ups range from 6 mo. to 2 yr.”

Savage, C., Savage, E., Fadiman, J., & Harman, W. (1964)

Ketamine and Depression

Intravenous ketamine therapy in a patient with a treatment-resistant major depression

“In summary, we found a single infusion of 0.5 mg/kg ketamine to have a strong antidepressant effect, which was not affected by a co-morbid abuse of benzodiazepines and alcohol. This suggests that infusion of ketamine might be a valuable treatment option for a wider range of patients than previously reported. Our results are in accordance with the previous findings of Berman et al. [3] and Zarate et al. [4]. The former found that four out of eight patients achieved an at least 50% reduction in HDRS scores over a three day period post infusion; the latter reported to have found 71% to respond- and 29% to remit on day one. Although our patient did not reach remission in the first 24 hours, we registered an improvement of 56.6% in the HDRS score over the course of two days post infusion. Similarly to the other studies, the onset of improvements was very rapid within minutes after ending the infusion. There is some speculation whether the presence and a certain intensity of psychomimetic effects are necessary for the antidepressant effects to occur [3]. Furthermore, it is not yet completely clear if directly targeting the NMDA receptor complex is essential for the dramatic and swift antidepressant effects. For further research we would therefore suggest to compare different dosages, different intervals of administration and different forms of application. In conclusion, ketamine seems to have a high potential in the treatment of refractory depression. Additional studies are certainly needed to confirm these preliminary findings.” Michael Liebrenza , Alain Borgeatb , Ria Leisingera , Rudolf Stohlera (2007)

Ketamine for Depression: Where Do We Go from Here?

Since publication of the first randomized controlled trial describing rapid antidepressant effects of ketamine, several reports have confirmed the potential utility of this dissociative anesthetic medication for treatment of major depressive episodes, including those associated with bipolar disorder and resistant to other medications and electroconvulsive therapy. These reports have generated several questions with respect to who might respond to ketamine, how, and for how long. To start answering these questions. We used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant effects of ketamine and of all recently completed, ongoing, and planned studies. To date, 163 patients, primarily with treatment-resistant depression, have participated in case studies, open-label investigations, or controlled trials. All controlled trials have used a within-subject, crossover design with an inactive placebo as the control. Ketamine administration has usually involved an anaesthesiologist infusing a single, subanesthetic, intravenous dose, and required hospitalization for at least 24 hours postinfusion. Response rates in the open-label investigations and controlled trials have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours postinfusion. Although adverse effects have generally been mild, some patients have experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk–benefit analyses support further research of ketamine for individuals with severe mood disorders. However, given the paucity of randomized controlled trials, lack of an active placebo, limited data on long-term outcomes, and potential risks, ketamine administration is not recommended outside of the hospital setting.

Marijeaan het Rota, Carlos A.ZarateJr.b, Dennis S.Charneyc, Sanjay J.Mathewde (2012)

Rapid Antidepressant Effect of Ketamine Anesthesia During Electroconvulsive Therapy of Treatment-Resistant Depression: Comparing Ketamine and Propofol Anesthesia

Background: Reports of the superiority of the antidepressant effect of ketamine during the conduct of electroconvulsive therapy (ECT) have been limited. We conducted an open-label trial of ketamineto determine whether ketamine as the anesthetic during ECT would provide a greater antidepressant effect than the antidepressant effect obtained with propofol.

Methods: Between April 2006 and April 2007, 31 inpatients with treatment-resistant depressiongave written consent for ECT and to participate in this study. An anesthesiologist who was unaware of the mental symptoms of the subjects assigned them to receive propofol or ketamine anesthetic according to the preferences of the patients, and the patients underwent 8 ECT sessions for 4 weeks. The Hamilton Depression Rating Scale (HDRS) was valuated before ECT and after the completion of the second, fourth, sixth, and eighth ECT sessions.

Results: The HDRS scores improved earlier in the ketamine group, with decreases in HDRS scores that were significantly greater in the ketamine group.

Conclusions: The results suggested that it is possible to improve symptoms of depression earlier by using ketamine anesthesia.

Okamoto, Nagahisa MD*; Nakai, Tetsuji MD, PhD†; Sakamoto, Kota MD*; Nagafusa, Yuko MD*; Higuchi, Teruhiko MD, PhD*; Nishikawa, Toru MD, PhD‡ (2010)

Ketamine for Treatment-Resistant Unipolar Depression

“Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action andsignificant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD.”

Sanjay J. Mathew, Asim Shah, Kyle Lapidus, Crystal Clark, Noor Jarun, Britta Ostermeyer, James W. Murrough (2012)

Drug and Alcohol Addiction / dependency recovery

Ketamine and Treatment of Alcoholism

“Ketamine is a prescription drug used for general anesthesia. In subanesthetic doses, it induces profound psychedelic experiences and hallucinations. The subanesthetic effect of ketamine was the hypothesized therapeutic mechanism in the authors' use of ketamine-assisted psychotherapy for alcoholism. The results of a controlled clinical trial demonstrated a considerable increase in efficacy of the authors' standard alcoholism treatment when supplemented by ketamine psychedelic therapy (KPT). Total abstinence for more than one year was observed in 73 out of Ill (65.8%) alcoholic patients in the KPT group, compared to 24% (24 out of 100 patients) of the conventional treatment control group (p<0.01). The authors' studies of the underlying psychological mechanisms of KPT have indicated that ketamine-assisted psychedelic therapy of alcoholic patients induces a harmonization of the Minnesota Multiphasic Personality Inventory (MMPI) personality profile, positive transformation of nonverbalized (mostly unconscious) self-concept and emotional attitudes to various aspects of self and other people, positive changes in life values and purposes. important insights into the meaning of life and anincrease in the level of spiritual development. Most importantly, these psychological changes were shown to favor a sober lifestyle. The data from biochemical investigations showed that the phannacological action of KPT affects both monoaminergic and opioidergic neurotransmitter metabolism, i.e., those neurochemical systems which are involved in the pathogenesis of alcohol dependence. The data from EEG computer-assisted analysis demonstrated that ketamine increases theta activity in cerebrocortical regions of alcoholic patients. This is evidence of the reinforcement of limbic cortex interaction during the KPT session.” E. M. Krupitsky & A. Y. Grinenko (1997) 

Psychedelic Therapy Utilizing LSD in the Treatment of the Alcoholic Patient: A Preliminary Report

“The rationale of psychedelic therapy with alcoholic patients is focused on the alienation-breaking potential of "peak" or psychedelic experiences induced with the aid of LSD. An exemplary LSD session report and MMPI data on 69 pilot patients are presented for illustration. While all present results indicate that psychedelic therapy does add significantly to presently available alcoholic rehabilitation resources, it is emphasized that safe and effective use of LSD requires specialized training.”

ALBERT A. KURLAND, SANFORD UNGER, JOHN W. SHAFFER, and CHARLES SAVAGE (2006) https://doi.org/10.1176/ajp.123.10.1202

Anxiety

Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review

“Anxiety and depression are some of the most common psychiatric symptoms of patients suffering with life-threatening diseases, often associated with a low quality of life and a poor overall prognosis. 5-HT2A-receptor agonists(serotonergic hallucinogens, ‘psychedelics’) like lysergic acid diethylamide (LSD) and psilocybin were first investigated as therapeutic agents in the 1960s. Recently, after a long hiatus period of regulatory obstacles, interest in the clinical use of these substances has resumed. The current article provides a systematic review of studies investigating psychedelics in the treatment of symptoms of existential distress in life-threatening diseases across different periods of research, highlighting how underlying concepts have developed over time. A systematic search for clinical trials from 1960 to 2017 revealed 11 eligible clinical trials involving a total number of N = 445 participants, of which 7 trials investigated the use of lysergic acid diethylamide (LSD) (N = 323), 3 trials investigated the use of psilocybin (N = 92), and one trial investigated the use of dipropyltryptamine (DPT) (N = 30). The 4 more recent randomized controlled trials (RCTs) (N = 104) showed a significantly higher methodological quality than studies carried out in the 1960s and 1970s. Evidence supports that patients with life threatening diseases associated with symptoms of depression and anxiety benefit from the anxiolytic and antidepressant properties of serotonergichallucinogens. Some studies anecdotally reported improvements in patients´ quality of life and reduced fear of death. Moreover, low rates of side effects were reported in studies that adhered to safety guidelines. Further studies are needed to determine how these results can be transferred into clinical practice.”

Simon Reiche, Leo Hermle, Stefan Gutwinski, Henrik Jungaberle, Peter Gasser, Tomislav Majić (2018)

“Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.”

Johnson, M.W. & Griffiths, R.R. Neurotherapeutics (2017) 14: 734. https://doi.org/10.1007/s13311-017-0542-y

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

“Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.”

Roland R Griffiths, Matthew W Johnson, Michael A Carducci, Annie Umbricht, William A Richards, Brian D Richards, Mary P Cosimano, Margaret A Klinedinst (2016)

MDMA and Anxiety

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA

“4-phosphorloxy-N,N-dimethyltryptamine (psilocybin) and methylenedioxymethamfetamine (MDMA), best known for their illegal use as psychedelic drugs, are showing promise as therapeutics in a resurgence of clinical research during the past 10 years. Psilocybin is being tested for alcoholism, smoking cessation, and in patients with advanced cancerwith anxiety. MDMA is showing encouraging results as a treatment for refractory post-traumatic stress disorder, social anxiety in autistic adults, and anxiety associated with a life-threatening illness. Both drugs are studied as adjuncts or catalysts to psychotherapy, rather than as stand-alone drug treatments. This model of drug-assisted psychotherapy is a possible alternative to existing pharmacological and psychological treatments in psychiatry. Further research is needed to fully assess the potential of these compounds in the management of these common disorders that are difficult to treat with existing methods.”

Prof Michael C Mithoefer MDa, Prof Charles S Grob MDb, Prof Timothy D Brewerton MDa

https://doi.org/10.1016/S2215-0366(15)00576-3Get rights and content

Post-Traumatic Stress Disorder

Psychedelic medicine: a re-emerging therapeutic paradigm

“In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes.1,2

The public is often well-versed in the potential harms of psychedelic drugs, but much of this knowledge is from cases involving patients who used illicit substances in unsupervised nonmedical contexts. We discuss the emerging research for therapeutic purposes involving human subjects, considering both the possible benefits and the potential harms of using psychedelic agents as adjuncts to psychotherapy or counselling for mental illness.”

Kenneth W. Tupper, Evan Wood, Richard Yensen and Matthew W. Johnson, 2015 

Complex-Post Traumatic Stress Disorder

Personality

Sanford ML Unger (1963) Mescaline, LSD, Psilocybin, and Personality Change a Review, Psychiatry, 26:2, 111-125, DOI: 10.1080/00332747.1963.11023344

Positive Psychology

Psychedelic usage has been shown in above therapeutic research to increase feelings of self-actualisation (Reference), mindfulness, a search for something higher, increased spirituality, and reported “greater awareness of ultimate reality”(Savage, 1964), increased empathy and connectivity, increase in feeling all emotional states, increased creativity as well as decreasing negative or pathological states and it could be argued that psychedelic usage is in itself a positive psychology intervention (PPI) in the right contexts, and could be used within a coaching context to further compound the benefits in terms of personal development, dependent on the goals within the coaching context. Relatively little research has been conducted in this area so far, however Millière et al. (2018) wrote the following interesting article:

Psychedelics, Meditation, and Self-Consciousness

“In recent years, the scientific study of meditation and psychedelic drugs has seen remarkable developments. The increased focus on meditation in cognitive neuroscience has led to a cross-cultural classification of standard meditation styles validated by functional and structural neuroanatomical data. Meanwhile, the renaissance of psychedelic research has shed light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD, whose effects are mainly mediated by agonism of serotonin receptors. Few attempts have been made at bridging these two domains of inquiry, despite intriguing evidence of overlap between the phenomenology and neurophysiology of meditation practice and psychedelic states. In particular, many contemplative traditions explicitly aim at dissolving the sense of self by eliciting altered states of consciousness through meditation, while classical psychedelics are known to produce significant disruptions of self-consciousness, a phenomenon known as drug-induced ego dissolution. In this article, we discuss available evidence regarding convergences and differences between phenomenological and neurophysiological data on meditation practice and psychedelic drug-induced states, with a particular emphasis on alterations of self-experience. While both meditation and psychedelics may disrupt self-consciousness and underlying neural processes, we emphasize that neither meditation nor psychedelic states can be conceived as simple, uniform categories. Moreover, we suggest that there are important phenomenological differences even between conscious states described as experiences of self-loss. As a result, we propose that self-consciousness may be best construed as a multidimensional construct, and that “self-loss,” far from being an unequivocal phenomenon, can take several forms. Indeed, various aspects of self-consciousness, including narrative aspects linked to autobiographical memory, self-related thoughts and mental time travel, and embodied aspects rooted in multisensory processes, may be differently affected by psychedelics and meditation practices. Finally, we consider long-term outcomes of experiences of self-loss induced by meditation and psychedelics on individual traits and prosocial behavior. We call for caution regarding the problematic conflation of temporary states of self-loss with “selflessness” as a behavioral or social trait, although there is preliminary evidence that correlations between short-term experiences of self-loss and long-term trait alterations may exist.”

Millière, R., Carhart-Harris, R. L., Roseman, L., Trautwein, F. M., & Berkovich-Ohana, A. (2018)

Okamoto, Nagahisa , Nakai, Tetsuji , Sakamoto, Kota , Nagafusa, Yuko , Higuchi, Teruhiko, Nishikawa, Toru (2010) ‘Rapid Antidepressant Effect of Ketamine Anesthesia During Electroconvulsive Therapy of Treatment-Resistant Depression: Comparing Ketamine and Propofol Anesthesia’ in The Journal of ECT: September 2010 - Volume 26 - Issue 3 - p 223-227 doi: 10.1097/YCT.0b013e3181c3b0aa

References

Carhart-Harris, Et al. (2016) Psilocybin for Depression Study. Imperial College London https://beckleyfoundation.org/psilocybin-for-depression-2/

Carhart-Harris, R, Kaelen, M.,   Whalley, MG,.  Bolstridge, M,  Feilding, A, . Nutt, DJ (2015) ‘LSD enhances suggestibility in healthy volunteers.’ Psychopharmacology, 232 (2015), pp. 785-794

Robin L Carhart-Harris & Guy M Goodwin (2017) ‘The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future’, Neuropsychopharmacology volume 42, pages 2105–2113 

Hofmann, A, . A Frey, H Ott, T Petr Zilka, F Troxler (1954) ‘Elucidation of the structure and the synthesis of psilocybin.’ Experientia, 14 (1958), pp. 397-399 Google Scholar

Hofmann, A. R Heim, A Brack, H Kobel (1958) Psilocybin, a psychotropic substance from the Mexican mushroom Psilicybe mexicana Heim, Experientia, 14, pp. 107-109 CrossRef

Johnson, M.W. & Griffiths, R.R. Neurotherapeutics (2017) 14: 734. https://doi.org/10.1007/s13311-017-0542-y

Krupitsky E. M . & A. Y. Grinenko (1997) Ketamine Psychedelic Therapy (KPT): A Review of the Results of Ten Years of Research, Journal of Psychoactive Drugs, 29:2, 165-183, DOI: 10.1080/02791072.1997.10400185

Michael Liebrenza , Alain Borgeatb , Ria Leisingera , Rudolf Stohlera (2007) Intravenous ketamine therapy in a patient with a treatment-resistant major depression. SWISS MED WKLY 2007;137:234–236 Available at: https://smw.ch/en/resource/jf/journal/file/view/article/smw/en/smw.2007.11852/3e0f2ebccc712b7225668d764d56d0caeddfeda3/smw_2007_11852.pdf/

Millière, R., Carhart-Harris, R. L., Roseman, L., Trautwein, F. M., & Berkovich-Ohana, A. (2018). Psychedelics, Meditation, and Self-Consciousness. Frontiers in psychology, 9, 1475. doi:10.3389/fpsyg.2018.01475. [Online] Available at : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137697/ \

Roland R Griffiths, Matthew W Johnson, Michael A Carducci, Annie Umbricht, William A Richards, Brian D Richards, Mary P Cosimano, Margaret A Klinedinst (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial in Journal of Psychopharmacology, 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513

Roseman Leor, Nutt David J., Carhart-Harris Robin L. (2018) ‘Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression’ in Frontiers in Pharmacology Vol 8 DOI=10.3389/fphar.2017.00974

Sanjay J. Mathew, Asim Shah, Kyle Lapidus, Crystal Clark, Noor Jarun, Britta Ostermeyer, James W. Murrough (2012) Ketamine for Treatment-Resistant Unipolar Depression. in CNS Drugs 26: 189. https://doi.org/10.2165/11599770-000000000-00000

Simon Reiche, Leo Hermle, Stefan Gutwinski, Henrik Jungaberle, Peter Gasser, Tomislav Majić (2018) ‘Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review’ Progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 81, Pages 1-10, ISSN 0278-5846 https://doi.org/10.1016/j.pnpbp.2017.09.012.

Thomas J. Riedlinger & June E. Riedlinger (1994) Psychedelic and Entactogenic Drugs in the Treatment of Depression, Journal of Psychoactive Drugs, 26:1, 41-55, DOI: 10.1080/02791072.1994.10472600

Marijeaan het Rota, Carlos A.ZarateJr.b, Dennis S.Charneyc, Sanjay J.Mathewde (2012) Ketamine for Depression: Where Do We Go from Here? in Biological Psychiatry, Volume 72, Issue 7, 1 October 2012, Pages 537-547

Tupper, Kenneth W., Wood,  Evan ., Yensen, Richard.  Johnson, Matthew W. (2015) Psychedelic medicine: a re-emerging therapeutic paradigm in CMAJ Oct 2015, 187 (14) 1054-1059; DOI: 10.1503/cmaj.141124

Sanford ML Unger (1963) Mescaline, LSD, Psilocybin, and Personality Change a Review, Psychiatry, 26:2, 111-125, DOI: 10.1080/00332747.1963.11023344

Savage, C., Savage, E., Fadiman, J., & Harman, W. (1964). LSD: Therapeutic Effects of the Psychedelic Experience. Psychological Reports, 14(1), 111–120. https://doi.org/10.2466/pr0.1964.14.1.111

Walter N. Pahnke, Albert A. Kurland, Sanford Unger, Charles Savage, Sidney Wolf & Louis E. Goodman (1970)Psychedelic Therapy (Utilizing LSD) with Cancer Patients, Journal of Psychedelic Drugs, 3:1, 63-75, DOI: 10.1080/02791072.1970.10471363

https://reader.elsevier.com/reader/sd/pii/S2215036616300876?token=06777CB8C599F6B0D2F3A4021C369F4D2A024160201236AA70E6DD236E32E32A3E1507DF38788551EBDBF30943B31E7B

AL Halberstadt, MA GeyerMultiple receptors contribute to the behavioral effects of indoleamine hallucinogens

Neuropharmacology, 61 (2011), pp. 364-381

ArticleDownload PDFView Record in ScopusGoogle Scholar

4

V Boulougouris, JC Glennon, TW RobbinsDissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats

Neuropsychopharmacology, 33 (2008), pp. 2007-2019

CrossRefView Record in ScopusGoogle Scholar

5

JA HarveyRole of the serotonin 5-HT(2A) receptor in learning

Learn Mem, 10 (2003), pp. 355-362

CrossRefView Record in ScopusGoogle Scholar

6

VA Vaidya, GJ Marek, GK Aghajanian, RS Duman5-HT2A receptor-mediated regulation of brain-derived neurotrophic factor mRNA in the hippocampus and the neocortex

J Neurosci, 17 (8) (1997), pp. 2785-2795

View Record in ScopusGoogle Scholar

7

T Buchborn, H Schroder, V Hollt, G GreckschRepeated lysergic acid diethylamide in an animal model of depression: normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling

J Psychopharmacol, 28 (2014), pp. 545-552

CrossRefView Record in ScopusGoogle Scholar

8

R Griffiths, W Richards, M Johnson, U McCann, R JesseMystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

J Psychopharmacol, 22 (2008), pp. 621-632

CrossRefView Record in ScopusGoogle Scholar

9

RL Carhart-Harris, M Kaelen, M Bolstridge, et al.The paradoxical psychological effects of lysergic acid diethylamide (LSD)

Psychol Med, 46 (2016), pp. 1379-1390

CrossRefView Record in ScopusGoogle Scholar

10

RL Carhart-Harris, D Erritzoe, T Williams, et al.Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin

Proc Natl Acad Sci USA, 109 (2012), pp. 2138-2143

CrossRefView Record in ScopusGoogle Scholar

11

PS Hendricks, CB Thorne, CB Clark, DW Coombs, MW JohnsonClassic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population

J Psychopharmacol, 29 (2015), pp. 280-288

CrossRefView Record in ScopusGoogle Scholar

12

TS Krebs, PO JohansenPsychedelics and mental health: a population study

PLoS One, 8 (2013), p. e63972

CrossRefGoogle Scholar

13

JC Bouso, D Gonzalez, S Fondevila, et al.Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study

PLoS One, 7 (2012), p. e42421

CrossRefGoogle Scholar

14

P Gasser, D Holstein, Y Michel, et al.Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases

J Nerv Ment Dis, 202 (2014), pp. 513-520

CrossRefView Record in ScopusGoogle Scholar

15

CS Grob, AL Danforth, GS Chopra, et al.Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Arch Gen Psychiatry, 68 (2011), pp. 71-78

CrossRefView Record in ScopusGoogle Scholar

16

L Osorio Fde, RF Sanches, LR Macedo, et al.Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

Rev Bras Psiquiatr, 37 (2015), pp. 13-20

Google Scholar

17

FA Moreno, CB Wiegand, EK Taitano, PL DelgadoSafety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder

J Clin Psychiatry, 67 (2006), pp. 1735-1740

CrossRefView Record in ScopusGoogle Scholar

18

MW Johnson, A Garcia-Romeu, MP Cosimano, RR GriffithsPilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction

J Psychopharmacol, 28 (2014), pp. 983-992

CrossRefView Record in ScopusGoogle Scholar

19

MP Bogenschutz, AA Forcehimes, JA Pommy, CE Wilcox, P Barbosa, RJ StrassmanPsilocybin-assisted treatment for alcohol dependence: a proof-of-concept study

J Psychopharmacol, 29 (2015), pp. 289-299

CrossRefView Record in ScopusGoogle Scholar

20

M Johnson, W Richards, R GriffithsHuman hallucinogen research: guidelines for safety

J Psychopharmacol, 22 (2008), pp. 603-620

CrossRefView Record in ScopusGoogle Scholar

21

PE Greenberg, AA Fournier, T Sisitsky, CT Pike, RC KesslerThe economic burden of adults with major depressive disorder in the United States (2005 and 2010)

J Clin Psychiatry, 76 (2015), pp. 155-162

CrossRefView Record in ScopusGoogle Scholar

22

BN GaynesIdentifying difficult-to-treat depression: differential diagnosis, subtypes, and comorbidities

J Clin Psychiatry, 70 (suppl 6) (2009), pp. 10-15

CrossRefView Record in ScopusGoogle Scholar

23

HA SackeimThe definition and meaning of treatment-resistant depression

J Clin Psychiatry, 62 (suppl 16) (2001), pp. 10-17

View Record in ScopusGoogle Scholar

24

E Studerus, A Gamma, FX VollenweiderPsychometric evaluation of the altered states of consciousness rating scale (OAV)

PLoS One, 5 (2010), p. e12412

CrossRefGoogle Scholar

25

AJ Rush, MH Trivedi, HM Ibrahim, et al.The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression

Biol Psychiatry, 54 (2003), pp. 573-583

ArticleDownload PDFView Record in ScopusGoogle Scholar

26

L Ibrahim, N DiazGranados, J Franco-Chaves, et al.Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study

Neuropsychopharmacol, 37 (2012), pp. 1526-1533

CrossRefView Record in ScopusGoogle Scholar

27

MW Johnson, RA Sewell, RR GriffithsPsilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

Drug Alcohol Depend, 123 (2012), pp. 132-140

ArticleDownload PDFView Record in ScopusGoogle Scholar

28

KR Bonson, JW Buckholtz, DL MurphyChronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans Neuropsychopharmacology, 14 (1996), pp. 425-436

ArticleDownload