OPEN Foundation

J. Halpern

The association of psychedelic use and opioid use disorders among illicit users in the United States

Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment-resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patients were assigned, double blind, to an MDMA or a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others’ emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into “many” or “few” such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy.

Corey, V. R., Pisano, V. D., & Halpern, J. H. (2016). Effects of 3, 4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting. The Journal of Nervous and Mental Disease. http://dx.doi.org/10.1097/NMD.0000000000000499

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Hallucinogen persisting perception disorder: what do we know after 50 years?

Abstract

‘Flashbacks’ following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as ‘Hallucinogen Persisting Perception Disorder (Flashbacks)’, or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term ‘flashbacks’ is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD.

Halpern, J. H., & Harrison, G. P. Jr. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109-119. http://dx.doi.org/10.1016/S0376-8716(02)00306-X
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Genuine and drug-induced synesthesia: a comparison

Abstract

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed.

Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Sinke, C., Halpern, J. H., Zedler, M., Neufeld, J., Emrich, H. M., & Passie, T. (2012). Genuine and drug-induced synesthesia: a comparison. Consciousness and cognition, 21(3), 1419-1434. http://dx.doi.org/10.1016/j.concog.2012.03.009
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Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs

Abstract

Aims: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias.

Design: We compared illicit ecstasy users and non-users while (1) excluding individuals with significant life-time exposure to other illicit drugs or alcohol; (2) requiring that all participants be members of the ‘rave’ subculture; and (3) testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons.
Setting: Field study.
Participants: Fifty-two illicit ecstasy users and 59 non-users, aged 18–45 years.
Measurements: Battery of 15 neuropsychological tests tapping a range of cognitive functions.
Findings: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users.
Halpern, J. H., Sherwood, A. R., Hudson, J. I., Gruber, S. Kozin, D., & Pope Jr., H. G. (2011). “Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction, 106(4), 777-786. http://dx.doi.org/10.1111/j.1360-0443.2010.03252.x
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The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Introduction

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6).

An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a non-hallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20 mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies [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”][…]

Karst, M., Halpern, J. H., Bernateck, M., & Passie, T. (2010). The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series. Cephalalgia, 30(9), 1140-1144. https://dx.doi.org/10.1177/0333102410363490
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The Pharmacology of Lysergic Acid Diethylamide: A Review

Abstract

Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so-called “experimental psychosis” by altering neurotransmitter system and in psychotherapeutic procedures (“psycholytic” and “psychedelic” therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments. Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho-) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers. The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill.

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(4), 295–314. http://dx.doi.org/10.1111/j.1755-5949.2008.00059.x
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Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament

Summary

Background: Ayahuasca is a South American hallucinogenic tea used as a sacrament by the Santo Daime Church, other religions, and traditional peoples. A recent U.S. Supreme Court decision indicates religious ayahuasca use is protected, but little is known about health consequences for Americans.

Material/Methods: 32 (out of 40) American members of one branch of the Santo Daime Church were interviewed providing demographic information, physical exam, drug use timeline, a variety of psychological measures, and data about childhood conduct disorder. Subjects were asked about extent of Church participation, what is liked least and most about ayahuasca, and what health benefi ts or harms they attribute to ayahuasca.

Results: Members usually attend services weekly (lifetime 269±314.7 ceremonies; range 20–1300). Physical exam and test scores revealed healthy subjects. Members claimed psychological and physical benefits from ayahuasca. 19 subjects met lifetime criteria for a psychiatric disorder, with 6 in partial remission, 13 in full remission, and 8 reporting induction of remission through Church participation. 24 subjects had drug or alcohol abuse or dependence histories with 22 in full remission, and all 5 with prior alcohol dependence describing Church participation as the turning point in their recovery.

Conclusions: Conclusions should not be extrapolated to hallucinogen abusers of the general public. For those who have religious need for ingesting ayahuasca, from a psychiatric and medical perspective, these pilot results substantiate some claims of benefi t, especially if subjects interviewed fully refl ect general membership. Further research is warranted with blinded raters, matched comparison groups, and other measures to overcome present study limitations.

Halpern, J. H., Sherwood, A. R., Passie, T., Blackwell, K. C., & Ruttenber, A. J. (2008). Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament. Medical Science Monitor, 14(8), SR15-SR22. PMID: 18668010

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Response of cluster headache to psilocybin and LSD

Abstract

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

Sewell, R. A., Halpern, J. H., & Pope, Jr., H. G. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 66(12), 1920–1922. http://dx.doi.org/10.1212/01.wnl.0000219761.05466.43
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Hallucinogenic botanicals of America: A growing need for focused drug education and research

Abstract

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Halpern, J. H., & Sewell, R. A. (2005). Hallucinogenic botanicals of America: A growing need for focused drug education and research. Life sciences, 78(5), 519-526. https://dx.doi.org/10.1016/j.lfs.2005.09.005
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