Ideal psychotropic drug may cause physical dependence

A report in the current issue of Psychotherapy and Psychosomatics by a group of European investigators headed by Fabrizio Schifano (UK) has explored the potential for dependence of pregabalin using patients' online reports.

Pregabalin is a prescription drug licensed to treat generalized anxiety disorder, partial epilepsy, and neuropathic pain. Pregabalin is structurally related to gabapentin and shares some therapeutic indications with clonazepam. However, both clonazepam and gabapentin possess an identified abuse potential, at least in selected populations. Between January 2008 and August 2010, qualitative Google searches of 203 websites have been carried out in 8 European languages using key words such as 'legal highs', 'research chemicals', 'online pharmacy', 'Lyrica', 'pregabalin', and 'online pharmacies'. Pregabalin was described as an 'ideal psychotropic drug' for recreational purposes to achieve specific mindsets, including: alcohol/GHB/benzodiazepine-like effects mixed with euphoria; to achieve entactogenic feelings and DXM-like disassociation, and to cope with opiate/opioid withdrawal. Misuse of pregabalin mostly seemed to occur orally, but intravenous, rectal ('plugging'), and 'parachuting' (emptying the content of the capsule into a pouch) self-administration techniques were also reported. Time of onset of the effects ranged between 10 min and 2 h, depending on the route of administration. Tolerance may reportedly develop fairly rapidly, and wear off quickly after drug cessation. Similarly, gabapentin seemed to possess both heavy sedative and psychedelic effects. Interestingly, however, one user argued that 'pregabalin outshines gabapentin. Far less dosage to achieve the same recreational high '. Similarly to pregabalin, drug tolerance could reportedly develop very rapidly. Conversely, clonazepam was reportedly inducing either sedation (at 1-2 mg) or stimulation (at more than 8 mg). Clonazepam was typically co-administered with different sedatives and/or psychedelics. Pregabalin, gabapentin and clonazepam were commonly offered for sale on the web, without the need of a prescription. One could wonder about the anxiolytic properties of pregabalin, gabapentin and clonazepam as potential mediators for misuse. In fact, some users might start self-administering with these GABAergic drugs as a way of self-medicating. Because of rapid development of high tolerance levels with both pregabalin and gabapentin, increasing dosages are self-administered. In line with observations presented in this paper, pregabalin is indeed characterized by higher (2.5 times) potency, quicker absorption rates, and greater bioavailability levels than gabapentin.

One could wonder why both gabapentin and pregabalin, in apparent contrast with clonazepam, seem to possess both a sedative as well as a dissociative effect. Although all 3 compounds are GABAergic, the precise mechanism of action of pregabalin and gabapentin is still unclear. Conversely, clonazepam is a well-characterized, powerful, compound which seems to have replaced flunitrazepam as the most popular misused benzodiazepine. A better clarification of the pregabalin misuse potential level is of interest, since the drug has recently been proposed as a treatment for substance misuse, for both alcohol- and benzodiazepine-dependent individuals. The potential of misuse of pregabalin is not typically mentioned in the prescribers' aids. However, controlled clinical studies carried out in over 5,500 patients have shown that in some patient populations self-reporting rates of euphoria ranged between 1 and 12%. Abrupt/rapid discontinuation of pregabalin may be associated with insomnia, nausea, headache, or diarrhea, which may be suggestive of physical dependence. One of the most interesting findings of the present report is the dissociative effect noticed among pregabalin/gabapentin abusers and not in clonazepam abusers.