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.
Study Arms & Interventions
Clonazepam
experimentalOpen-label administration of clonazepam for 2 months, followed by a gradual taper and a 6-month follow-up.
Interventions
- Placebo0.25 mgvia oral• twice daily
Initial titration phase: started at 0.25 mg b.i.d., individually raised up to 2 mg b.i.d. by the end of the first week.
- Placebo2 mgvia oral• daily
Maintenance phase: 2 mg/day for the remainder of the 2-month treatment period.
- Placebo0.5 mgvia oral• weekly• 4 doses total
Discontinuation phase: 0.5 mg weekly over 1 month to prevent rebound-relapse symptoms.
Primary Results(1 publication)
Participants
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Clonazepamexperimental | 16 | — | — | — | 2(12.5%) |
* Two patients dropped out of treatment before the end of the 2-month investigation and were removed from the sample. No specific adverse event counts or types were reported, though the study notes clonazepam was 'well tolerated' and mentions 'mild temporary daytime sedation and mild psychomotor impairment' as the more frequent reported side-effects.