Gamma-Hydroxybutyric acid

Alternative names

γ-hydroxybutyric acid

ECDD Recommendation
Rescheduled from Schedule IV to Schedule II of the 1971 Convention on Psychotropic substances
Recommendation (from TRS)
Substance identification and pharmacodynamics
γ-Hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid and sodium oxybate, is a naturally occurring substance found in low concentrations in mammalian tissues. It is considered to act by binding to GHB-specific receptors and γ-aminobutyric acid B (GABAB) receptors. At pharmacological doses it acts as a central nervous system depressant.

Previous reviews
GHB was pre-reviewed during the thirty-first (15) and thirty-second (16) meetings, held in 1998 and 2000, respectively. In 2001, GHB was placed in Schedule IV of the 1971 Convention by a decision of the CND. It was again pre-reviewed at the thirty-fourth ECDD meeting in 2006 (6), at which time the Expert Committee recommended a new critical review to consider its possible rescheduling.

Evidence on dependence potential
The Expert Committee examined additional information from the updated critical review report and peer-review reports. The Expert Committee noted that there is compelling evidence that dependence on GHB exists in humans and noted withdrawal syndromes and withdrawal seizures.

Actual abuse
The Expert Committee noted that at present, GHB appears to be mainly used and abused in the United States of America, Europe and Australia. Most GHB used illicitly originates from clandestine manufacture. In their discussions, the Expert Committee and advisers agreed on the narrow margin of safety of GHB. There have been numerous reports from Europe and the United States of accidental fatal and non-fatal overdoses where GHB was implicated, both when used alone and with other substances. The Expert Committee also noted there have been reports of GHB being used to facilitate sexual assault.

Therapeutic usefulness
GHB is used as a medicine in some countries on a small scale for various indications. GHB is not included in the WHO Model List of Essential Medicines (17).

Need for the substance for other purposes (e.g., industrial)
The Expert Committee acknowledged the use of GHB in the production of a wide variety of industrial polymers.

Measures taken by countries to curb abuse
The Expert Committee was made aware of measures taken by 30 out of the 51 countries that responded to the questionnaire circulated by WHO in 2008 in preparation for the meeting. For example, Norway is planning to implement legal limits for driving under the influence of non-alcohol drugs including GHB. In the United States, GHB (Xyrem®) is available for the treatment of narcolepsy in association with an extensive risk management programme. Postmarketing data from this programme show minimal abuse or diversion of this product. The Netherlands recently re-assessed the risk potential of GHB and found it to be moderate to high. On this basis GHB was upgraded to List 1 (hard drugs) of the Dutch Opium Act.

The Expert Committee considered the implications of rescheduling this substance. On the basis of available data on its toxicity and dependence potential, the Committee rated the abuse liability of GHB to be substantial, whereas the therapeutic usefulness is little to moderate. The Committee therefore came to the conclusion that GHB should be moved from Schedule IV to Schedule II of 1971 Convention.