Trial PaperAnxiety DisordersLSD

Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features

This open-label study (n=16) suggests that high-potency benzodiazepines like clonazepam (2mg/day for 60 days) may help alleviate Hallucinogen Persisting Perception Disorder (HPPD). The patients reported relief up to four months after treatment. Do note that there was no control group in this study.

Authors

  • Gelkopf, M.
  • Skladman, I.
  • Rudinski, D.

Published

International Clinical Psychopharmacology
individual Study

Abstract

A unique and intriguing characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appear during the intoxication, in the absence of recent intake of hallucinogens. Hallucinogen persisting perception disorder (HPPD) is a condition in which the re-experiencing of one or more perceptual symptoms causes significant distress or impairment in social, occupational or other important areas of functioning and may be extremely debilitating. Benzodiazepines are one of the recommended agents for the treatment of HPPD but it is unclear which of them may be more helpful. The goal of our investigation was to assess the efficacy of clonazepam in the treatment of LSD-induced HPPD. Sixteen patients fulfilled entrance criteria. All complained of HPPD with anxiety features for at least 3 months and were drug free at least 3 months. They received clonazepam 2 mg/day for 2 months. Follow-up was continued for 6 months. They were weekly evaluated during the 2 months of clonazepam administration and monthly during the follow-up period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Patients reported a significant relief and the presence of only mild symptomatology during the clonazepam administration. This improvement was clearly sustained and persisted during a 6-month follow-up period. This study suggests that high potency benzodiazepines like clonazepam, which has serotonergic properties, may be more effective than low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD.

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Research Summary of 'Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features'

Introduction

Hallucinogen persisting perception disorder (HPPD) refers to the long-term recurrence of perceptual disturbances that resemble symptoms experienced during acute lysergic acid diethylamide (LSD) intoxication. The Introduction distinguishes between benign, transient “flashback” phenomena experienced by some users and HPPD, which is persistent, distressing and can cause substantial functional impairment. The authors summarise hypothesised mechanisms for HPPD, including LSD’s 5-HT2 partial agonist effects, enhanced glutamatergic transmission, damage or dysfunction of cortical serotonergic inhibitory interneurons (with GABAergic outputs) producing chronic disinhibition of visual processing, reverse tolerance or sensitisation after exposure, and possible familial or genetic predisposition. This study set out to evaluate clonazepam, a high-potency benzodiazepine with reported serotonergic properties, in the treatment of LSD-induced HPPD with co-occurring anxiety features. The investigation responds to clinical uncertainty about which benzodiazepines are most effective for HPPD and aims to assess symptomatic change during a fixed pharmacological trial and over a 6-month follow-up period.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topic
  • APA Citation

    Lerner, A. G., Gelkopf, M., Skladman, I., Rudinski, D., Nachshon, H., & Bleich, A. (2003). Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features. International Clinical Psychopharmacology, 18(2), 101-105. https://doi.org/10.1097/00004850-200303000-00007

Related Clinical Trial

Completed

Clonazepam Treatment of LSD-Induced Hallucinogen Persisting Perception Disorder with Anxiety Features: An Open-Label Prospective Case Series

Open-label prospective single-arm case series (Lev Hasharon Mental Health Medical Center, Pardessya, Israel / Sackler Faculty of Medicine, Tel-Aviv University) of fixed-dose clonazepam 2 mg/day over 2 months in 16 young adults (11M/5F, ages 17–24, mean 21.1) meeting DSM-IV criteria for LSD-induced Hallucinogen Persisting Perception Disorder (HPPD) with anxiety features. All participants had a polysubstance-use history (cannabis, MDMA, LSD) but identified LSD as the trigger, reported HPPD symptoms for ≥3 months, and were drug-free for ≥3 months (confirmed by random weekly urine screens). Prior trials with short-acting low-potency benzodiazepines had failed or caused side-effects. Dosing was titrated from 0.25 mg b.i.d. on day 1 up to 2 mg/day over the first week to minimise side-effects, maintained for 2 months, then tapered by 0.5 mg weekly over 1 month. Follow-up continued for 6 months after discontinuation. Outcomes: Clinical Global Impression Scale (CGI), a Self-Report Scale (SRS) for HPPD severity, and the Hamilton Anxiety Rating Scale (HAM-A) — assessed weekly during the 8-week treatment and monthly during the 6-month follow-up. Two patients dropped out before 2 months, leaving n=14 analysed. No registry entry: the trial pre-dates the ICMJE 2005 registration mandate and no IRB protocol ID is reported in the paper.

Started
Type
interventional
Randomized
No
Registry ID
LERNER-2003-ICP-CLONAZEPAM-HPPD

References (1)

Papers cited by this study that are also in Blossom

The psychopharmacology of hallucinogens

Abraham, H. D., Aldridge, A. M., Gogia, P. · Neuropsychopharmacology (1996)

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