Between 1997 and 2011, more than 200 new substances were notified through the early-warning system, with the record number of 49 novel molecules reported in 2011. The pattern of acute toxicity associated with the consumption of these new substances is generally similar to that seen with traditional drugs of abuse. Recently, a new class of synthetic stimulants closely related to pyrrolidine and piperidine compounds and known as pipradrol derivatives appeared in the recreational drug market. These substances, producing amphetamine-like effects, are used by people in substitution of traditional illicit drugs. The aim of this paper is to summarize the clinical, pharmacological and toxicological information currently available about this new class of synthetic drugs of abuse.
Highlights
► Pipradrol, 2-DPMP, D2PM and desoxy-D2PM are a new class of designer drugs of abuse. ► These substances are marketed as legal highs. ► Pipradrol, 2-DPMP, D2PM and desoxy-D2PM are used as alternative to other illicit stimulants. ► These drugs can produce prolonged neuropsychiatric effects. ► Literature data suggest a high risk of central nervous and cardiovascular system toxicity.
In recent years, the spread of new designer drugs of abuse is continually on the rise (Gibbons, 2012). Between 1997 and 2011, more than 200 new substances were notified through the early-warning system, with the record number of 49 novel molecules reported in 2011 (rednetproject, 2012). These substances, generally marketed as “legal highs”, are used by people in place of the traditional illicit drugs because they can produce the same psychotropic effects (Zawilska, 2011). The term “legal highs” is applied to a wide range of vegetable derivatives or synthetic substances specifically used to circumvent existing drug controls (EMCDDA, 2011). In the last years, there have been numerous reports of severe acute intoxications and deaths related to the consumption of many unconventional drugs of abuse (Wood et al., 2010, Wood et al., 2011a, Murray et al., 2012a, Murray et al., 2012b, Shanks et al., 2012). The pattern of acute toxicity associated with the consumption of these new substances is generally similar to that seen with traditional drugs of abuse (Wood et al., 2008). This new trend, combined with the ability of the internet drug market to disseminate novel recreational products quickly, has raised concern in the international scientific community (Vardakou et al., 2011, Jones, 2010). Recently, a new class of synthetic stimulants closely related to pyrrolidine and piperidine compounds and known as pipradrol derivatives appeared in the recreational drug market (droganews.it/2472, 2011, droganews.it/2481, 2011, EMCDDA, 2011). These stimulants, consumed by people for their amphetamines-like effects (drugs-forum.org, 2007, psychonaut.com, 2011), principally include: pipradrol, desoxypipradrol (2-DPMP), diphenylproplinol (D2PM) and diphenylmethylpyrrolidine (desoxy D2PM). Although the popularity of these novel stimulants is increasing among drug users, there are limited information on their acute and chronic human toxicity. In addition, there are no studies about the real spread of pipradrol derivatives in recreational products sold in head shops and webshops. The aim of this paper is to summarize the clinical, pharmacological and toxicological information currently available about this new class of synthetic drugs of abuse.
Methods
Literature searches were performed using the following electronic databases: PubMed, Embase, PsycINFO, Cochrane database. The keywords used were: pipradrol, desoxypipradrol, diphenylproplinol, 2-DPMP, D2PM, diphenylmethylpyrrolidine, legal highs, Ivory Wave, A3A Methano, and Head Candy. Furthermore, in order to conduct a research of data as extensively as possible, we also explored the information present within the unconventional references such as web communities, and drug forums. No
Chemistry
Pipradrol, IUPAC name diphenyl(piperidin-2-yl)methanol, and its desoxy form 2-DPMP, IUPAC name 2-benzhydryl-1-methylpiperidine, are based on a six membered piperidine ring, while D2PM, IUPAC name diphenyl(pyrrolidin-2-yl)methanol, and its desoxy form desoxy-D2PM, IUPAC name (RS)-2-(diphenylmethyl)pyrrolidine, are based on a five membered pyrrolidine ring. These compounds are structurally related to β-phenylmethylamphetamine, a potent stimulant with a long half life. However, they differ from
Pharmacology
There is a paucity of information on the pharmacological properties of pipradrol derivatives. In vitro study has shown that pipradrol inhibits the reuptake of and stimulates the release of dopamine and norepinephrine. In these pharmacodynamic actions it is less potent than d-amphetamine (Robbins et al., 1983). 2-DPMP inhibits the reuptake of and stimulates the release of dopamine and norepinephrine into purified synaptic vesicles of whole rat brain, rat striatum and rat hypothalamus (Ferris and
Toxicology
There are no studies on the toxicological effects of pipradrol derivatives in human. Recently, have been reported some confirmed cases of severe acute intoxication after consumption of legal highs containing pipradrol derivatives. In particular, there have been reports of acute toxicity related with the consumption of 2-DPMP from both Scotland and Ireland (hpa.org, 2011, eapcct.org, 2011). Clinical presentation was similar to amphetamine toxicity, but with predominant neuropsychiatric symptoms
Medical use
Pipradrol was developed in 1940s for treating obesity, depression, attention deficit hyperactivity disorder and narcolepsy. It was made illegal in many countries in 1970s due to its abuse potential Pipradrol is classified under the Misuse of Drugs Act as a Class C substance (enotes.com, 2012). 2-DPMP was developed by Ciba-Geigy (Novartis) in 1953 for treating ADHD, depression, narcolepsy and to be used to wake patients following anaesthesia. It is not currently used for therapeutic purpose (
Patterns of use
Recently, pipradrol derivatives have been found in recreational products such as Ivory Wave, 3A3 Methano, Head Candy and Whack. In some package, these substances have been combined with other psychoactive molecules such as glaucine and flurotropacocaine (Wood et al., 2011b, Lidder et al., 2008). D2PM and 2-DPMP have been found as a white powder that is generally taken by nasal insufflation or swallowing after wrapping the powder in a cigarette paper to avoid any unpleasant taste (ACMD, 2011).
Discussion
At present, there is a lack of toxicological information on pipradrol, D2PM, desoxy-D2PM and 2-DPMP in the scientific literature. Clinical information currently available suggests that these substances can produce the same psychotropic effects of other stimulants, but with a longer duration of action. This pharmacological characteristic combined with the legal status of pipradrol derivatives in some countries could encourage people who want to use stimulants, but are afraid of the legal
Conclusion
Although limited, the information currently available suggests that pipradrol derivatives are central nervous system stimulants producing prolonged neuropsychiatric effects. They are not controlled drugs in several countries and thus, they are sold as legal highs in head shops or web shops. Like synthetic cannabinoids and synthetic cathinones, these substances possess all the characteristics to become a popular new class of drugs of abuse. Scientific community must remain vigilant in order to
Conflict of interest statement
The authors declare that there are no conflicts of interest.