rTMS in the treatment of drug addiction: An update about human studies.

Drug addiction can be a devastating and chronic relapsing disorder with social, psychological and physical consequences, and more effective treatment options are needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has been assessed in a growing number of studies for its therapeutic potential in treating addiction. This review paper offers an overview on the current state of clinical research in treating drug addiction with rTMS. Because of the limited research in this area, all studies (including case reports) that evaluated the therapeutic use of rTMS in nicotine, alcohol or illicit drug addiction were included in this review. Papers published prior to December 2012 were found through an NCBI PubMed search (http://www.ncbi.nlm.nih.gov). A total of eleven studies were identified that met review criteria. There is nascent evidence that rTMS could be effective in reducing cocaine craving, and nicotine and alcohol craving and consumption, and might represent a potential therapeutic tool for treating addiction. Further studies are needed to identify the optimal parameters of stimulation for the most effective treatment of drug addiction, to improve our comprehension of the treatment neurophysiological effects, and to conduct rigorous, controlled efficacy studies with adequate power

Psychostimulant effect of the synthetic cannabinoid JWH-018 and AKB48: Behavioral, neurochemical, and dopamine transporter scan imaging studies in mice

JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB1 receptor blockade and dopamine (DA) D1/5 and D2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [123I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [3H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health

The Italian National Early Warning System for Drugs of Abuse: Toxicovigilance on New Psychoactive Substances

The National Early Warning System (NEWS) was created to identify new sentinel cases on new drugs of abuse, to collect and evaluate the few available clinical features, to diffuse clinical signals to the health system, and to promote preventative and regulatory actions

Synthetic cannabinoid JWH-018 impairs object recognition memory in mice: behavioral and electrophysiological evidence

Introduction: JWH-018 (1-pentyl-3-(1-naphthoyl) indole) is a synthetic CB1 and CB2 agonist illegally marketed in 'Spice' and “herbal blend” for its psychoactive effects similar to those produced by Cannabis. In rodents JWH-018 reproduces the typical effects of THC as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on memory functions are still unknowns. Behavioral and in vitro electrophysiological studies were undertaken to investigated the effects of acute JWH-018 administration on novel object recognition memory and hippocampal LTP formation in CD-1 male mice. Methods and Results: The novel object recognition task is a one-trial learning paradigm allowing the assessment of acquisition, consolidation or retrieval of (object) information separately. JWH-018 (0.1-1 mg/Kg i.p.) dose-dependently impaired both short (2 hours after training section) and long (24 hours after training section) memory retention in mice by CB1 receptor stimulation, since JWH-018 effect was prevented by the selective CB-1 receptor antagonist AM251 (3 mg/Kg). Electrically evoked Schaffer area fEPSP has been extracellularly recorded from stratum radiatum of mouse dorsal hippocampal transversal slices. A stimulus–response curve was recorded before and after JWH-018 contact. At this time, an LTP stimulation paradigm was applied. JWH-018 (10-1000 nM) dose-dependently reduced LTP in hippocampal slices and abolished it at higher concentrations (300 and 1000 nM). Conclusion: These results show that JWH-018 impairs cognitive function in mice possibly by impairing hippocampal memory formation. This aspect should be carefully investigated since chronic consumption of THC impairs cognitive function not only in animal models but in particular in human consumers by altering brain neurodevelopment (http://www.dronet.org/monografia.php?monografie=93)

Powerful cocaine-like action of MDPV on aggressive behaviour in isolated mice

MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone illegally marketed as “bath salts” or “plant food” and consumed for its psychostimulant effects similar to those produced by cocaine, amphetamines and MDMA. Clinical reports indicate that MDPV produce euphoria, increase alertness and at high doses it causes agitation, psychosis, tachycardia and even death (1). In particular, the second leading cause of death induced by MDPV and other cathinones is associated with self-harm, risky and violent behavior (2, 3). Anecdotal reports suggests that MDPV increases violent aggressive behavior in men similar to that reported for alcohol and cocaine consumption (4). In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, showing a greater potency compared to cocaine (5). Nevertheless, its role on aggressive behavior is still unknowns. Therefore, the aim of this study was to evaluate the effect of MDPV on aggressive behavior in mice and to compare its action with that induced by cocaine. The Resident-Intruder paradigm in isolated mice (6) was undertaken to investigate the effect of MDPV and cocaine on aggressive behavior. Saline administration causes an increase in aggressive behavior in 7% of total mice (n=50) with an increase of bite frequency of +52±1% respect to control baseline. Systemic MDPV administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 46% and 55 % of total mice (n=50 for each treatment) with an increased frequency of bites of +134±22% and +155±18 % respectively. Similarly, cocaine administration (i.p.) at 0.1 and 10 mg/Kg causes an increased aggressive behavior in 13% and 27 % of total mice (n=50 for each treatment) with an increased frequency of bites of +82±8% and +132±11 % respectively, proving to be less potent than MDPV in inducing aggressive behavior in mice. The aggressive effect caused by MDPV is consistent with the positive modulation on catecholamine release (5) and its powerful action may reflect its stronger ability to inhibit dopamine and norepinephrine uptake respect to cocaine (5). These results show for the first time that MDPV enhance aggressive behavior in mice with grater potency compared to cocaine. This aspect should be carefully investigated for the prevention of interpersonal violence in human induced by novel psychoactive drug consumption. (1) Prosser J.M. and Nelson L.S. (2012) J Med Toxicol. 8: 33-42. (2) Marinetti L.J. and Antonides H.M. (2013) J. Anal. Toxicol. 37: 135-146. (3) Schifano F., Corkery J. and Ghodse A.H. (2012) J. Clin. Psychopharmacol. 32: 710-714. (4) Chermack S.T. and Blow F.C. (2002) Drug Alcohol Depend. 58: 43-54. (5) Baumann M.H., Partilla J.S., Lehener K.R. et al., (2013) Neuropsychopharmacology 38:552-562. (6) Miczec K.A. and O’Donnel J.M. (1978) Psychopharmacology 57: 47-5

Neuropharmacology of New psychoactive substances (NPS): Focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants

New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, “dark net”) as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments). The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%)(WDR, 2014). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated with “Spice” use, will be described (De Luca et al., 2015a). Considering the growing evidence of a widespread use of NPS, this review will be useful to understand the new trends in the field of drug reward and drug addiction by revealing the rewarding properties of NPS, and will be helpful to gather reliable data regarding the abuse potential of these compounds.New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, "dark net") as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: Cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated with "Spice" use, will be described (De Luca et al., 2015a). Considering the growing evidence of a widespread use of NPS, this review will be useful to understand the new trends in the field of drug reward and drug addiction by revealing the rewarding properties of NPS, and will be helpful to gather reliable data regarding the abuse potential of these compounds

Cannabis e danni alla salute

Il lavoro rappresenta una sintesi degli studi scientifici relativi ai principali effetti dell\u2019uso di cannabis e dei suoi derivati sulla salute dell\u2019uomo