OPEN Foundation

Psychology

Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up

Abstract

Seventy detoxified heroin-addicted patients were randomly assigned to one of two groups receiving ketamine psychotherapy (KPT) involving two different doses of ketamine. The patients of the experimental group received existentially oriented psychotherapy in combination with a hallucinogenic (“psychedelic”) dose of ketamine (2.0 mg/kg im). The patients of the control group received the same psychotherapy combined with a low, non-hallucinogenic (non-psychedelic), dose of ketamine (0.2 mg/kg im). Both the psychotherapist and patient were blind to the dose of ketamine. The therapy included preparation for the ketamine session, the ketamine session itself, and the post session psychotherapy aimed to help patients to integrate insights from their ketamine session into everyday life. The results of this double blind randomized clinical trial of KPT for heroin addiction showed that high dose (2.0 mg/kg) KPT elicits a full psychedelic experience in heroin addicts as assessed quantitatively by the Hallucinogen Rating Scale. On the other hand, low dose KPT (0.2 mg/kg) elicits “sub-psychedelic” experiences and functions as ketamine-facilitated guided imagery. High dose KPT produced a significantly greater rate of abstinence in heroin addicts within the first two years of follow-up, a greater and longer-lasting reduction in craving for heroin, as well as greater positive change in nonverbal unconscious emotional attitudes than did low dose KPT.

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(4), 273-283. http://dx.doi.org/10.1016/S0740-5472(02)00275-1
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Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers

Abstract

Aims: Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and β-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity.

Methods: Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg−1 body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS).

Results: Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were −20.20±15.23 µV2 and −2.70±2.21 µV2 for total power and theta power, respectively. Relative power decreased in the delta (−1.20±1.31% after 120 min at P3) and theta (−3.30±2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00±0.88% after 90 min at P3) and beta-4 (0.30±0.24% after 90 min at P3) subbands. Finally, an increase was also seen for the centroid of the total activity and its deviation. EEG modifications began as early as 15–30 min, reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4–6 h after administration.

Conclusions: The central effects of ayahuasca could be objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of previously reported subjective effects. The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system.

Riba, J., Anderer, P., Morte, A., Urbano, G., Jané, F., Saletu, B., & Barbanoj, M. J. (2002). Topographic pharmaco‐EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. British journal of clinical pharmacology, 53(6), 613-628. 10.1046/j.1365-2125.2002.01609.x
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Flashback and Hallucinogen Persisting Perception Disorder: clinical aspects and pharmacological treatment approach.

Abstract

One unique characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appeared during the intoxication after the immediate effect of the hallucinogen has worn off. This recurring syndrome, mainly visual, has not been clearly understood, appreciated or distinguished from other clinical entities by clinicians. The terms Flashback and Hallucinogen Persisting Perception Disorder (HPPD) are used interchangeably in the professional literature. Flashback is a usually short-term, non-distressing, spontaneous, recurrent, reversible and benign condition accompanied by a pleasant affect. In contrast, HPPD is a generally long-term, distressing, spontaneous, recurrent, pervasive, either slowly reversible or irreversible, non-benign condition accompanied by an unpleasant dysphoric affect. Flashback and HPPD appear to be part of a vast and broad spectrum of non-psychopathological and psychopathological states reported by hallucinogen users. Pharmacological agents such as clonidine, perphenazine and clonazepan have been shown to ameliorate this syndrome in some of the individuals seeking treatment.

Lerner, A. G., Gelkopf, M., Skladman, I., & Oyffe, I. (2002). Flashback and hallucinogen persisting perception disorder: clinical aspects and pharmacological treatment approach. The Israel journal of psychiatry and related sciences, 39(2), 92.
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No Difference in Brain Activation During Cognitive Performance Between Ecstasy (3,4-Methylenedioxymethamphetamine) Users and Control Subjects: A [H215O]-Positron Emission Tomography Study

Abstract

The long-term use of the serotonin-releaser and uptake-inhibitor 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) has been associated with memory impairments and increased liability to depressive mood and anxiety attacks. It is unclear, however, whether these psychologic deviations are reflected in alterations of the underlying neurophysiologic substrate. The authors compared mood and regional cerebral blood flow (rCBF) profiles between regular polytoxic Ecstasy users and Ecstasy-naive controls. Brain activity as indexed by rCBF was measured during cognitive activation by an attentional task using positron emission tomography and [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”][H2(15)O]. Mood was assessed by means of the Hamilton Rating Scale for Depression (HAM-D) and the EWL Mood Rating Scale. Statistical parametric mapping revealed that brain activity did not differ between the two groups. Both groups also performed equally on the cognitive task requiring sustained attention. However, significantly higher levels of depressiveness as determined by the HAM-D and EWL scales were found in Ecstasy-using subjects. These data indicate that, despite differences in mood, polytoxic Ecstasy users do not differ from Ecstasy-naive controls in terms of local brain activity. Heightened depressiveness in the Ecstasy group was consistent with results from previous studies and could be related to serotonergic hypofunction resulting from repeated MDMA consumption. However, this study cannot exclude the possibility that the observed differences are preexisting rather than a result of Ecstasy use.

 

Gamma, A., Buck, A., Berthold, T., & Vollenweider, F. X. (2001). No difference in brain activation during cognitive performance between ecstasy (3, 4-methylenedioxymethamphetamine) users and control subjects: a [H215O]-positron emission tomography study. Journal of clinical psychopharmacology, 21(1), 66-71. http://dx.doi.org/10.1097/00004714-200102000-00012

 

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Deconstructing Ecstasy: The Politics of MDMA Research

Abstract

What is Ecstasy? Defined by the New Webster’s Dictionary as a state of intense overpowering emotion, a condition of exultation or mental rapture induced by beauty, music, artistic creation, or the contemplation of the divine, ecstasy derives etymologically from the ancient Greek ekstasis, which means flight of the soul from tbe body. The anthropologist, Mircea Eliade, who explored the roots of religious experience in his book Shamanism: Archaic Techniques of Ecstasy, has described the function of this intense states of mind among aboriginal peoples. Select individuals are called to become shaman, a role specializing, in inducing ecstastic states of trance where the soul is believed to leave the body and ascend to the sky or descend to the underworld. The shaman is thus considered a ‘technician of the sacred’, having been initiated through a process of isolation, ritual solitude, suffering and the imminence of death. Such initiation into the function of ecstatic states of consciousness, always accompanied by comprehensive tutelage from tribal elders, allows the shaman to assume for his tribal group the vital role of intermediary, or conduit, between the profane world of everyday existence and the sacred domains of alternative reality (Eliade, 1951; Schultes and Hofmann 1992)

Grob, C. S. (2000). Deconstructing Ecstasy: The Politics of MDMA Research. Addiction Research & Theory, 8(6), 549-588. http://dx.doi.org/10.3109/16066350008998989
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LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study.

Abstract

A pilot open study was conducted in order to evaluate the efficacy of clonidine in the treatment of LSD-induced hallucinogen persisting perception disorder (HPPD). Eight patients fulfilled entrance criteria. All complained of HPPD for at least 3 months and were drug free at least 3 months. They received fixed low doses of clonidine, 0.025 mg, three times a day for 2 months. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms (graded 0-5). Patients scored an average of 5.25 (SD = 0.46) on the CGI and 4 on the self-report scale at baseline, indicating marked psychopathology. One patient dropped out at week 3 and a second patient dropped out at week 5. Of the six patients remaining at the end of 2 months, the average CGI score was 2.5 (SD = 0.55) and the self-report scale score was 2, indicating mild symptomatology. LSD-related flashbacks associated with excessive sympathetic nervous activity may be alleviated with clonidine in some patients.

Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., Sigal, M., & Weizman, A. (2000). LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study. International clinical psychopharmacology, 15(1), 35-37.
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Role of Serotoninergic Neurons and 5-HT Receptors in the Action of Hallucinogens

Abstract

Brain serotonin receptors and serotoninergic pathways have received increasing attention as targets for a wide variety of therapeutic agents. Perhaps peculiar to this realm, however, are the so-called hallucinogenic drugs, which presently lack demonstrated therapeutic utility, and still remain, as they have for at least the past 50 years, pharmacological curiosities. Research into their mechanism of action is generally poorly funded, and we know relatively little about how they affect the brain, despite their continued popularity as recreational drugs among a significant proportion of the population.

Nichols, D. E. (2000). Role of serotoninergic neurons and 5-HT receptors in the action of hallucinogens. In Serotoninergic Neurons and 5-HT Receptors in the CNS (pp. 563-585). Springer Berlin Heidelberg. http://dx.doi.org/10.1007/978-3-642-60921-3_21

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Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness

Abstract

Daily events that boost the immune system (as indicated by levels of salivary immunoglobulin A), some instances of spontaneous remission, and mystical experiences seem to share a similar cluster of thoughts, feelings, moods, perceptions, and behaviors. Entheogens – psychedelic drugs used in a religious context – can also produce mystical experiences (peak experiences, states of unitive consciousness, intense primary religious experiences) with the same cluster of effects. When this happens, is it also possible that such entheogen-induced mystical experiences strengthen the immune system? Might spontaneous remissions occur more frequently under such conditions? This article advances the so called “Emxis hypothesis” – that entheogen-induced mystical experiences influence the immune system.

Roberts, T. B. (1999). Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness. Advances in Mind-Body Medicine, 15, 139-147.
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Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action

Abstract

Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.

Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F., Bäbler, A., Vogel, H., & Hell, D. (1998). Psilocybin induces schizophrenia‐like psychosis in humans via a serotonin‐2 agonist action. Neuroreport, 9(17), 3897-3902. https://dx.doi.org/doi:10.1097/00001756-199812010-00024
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Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

Abstract

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 111 (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 an increase 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 pharmacological 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 KPT session.

Krupitsky, E. M., & Grinenko, A. Y. (1997). Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Journal of psychoactive drugs, 29(2), 165-183. https://dx.doi.org/10.1080/02791072.1997.10400185

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30 April - Q&A with Rick Strassman

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