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Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

Miliano C, Serpelloni G, Rimondo C, Mereu M, Marti M, De Luca MA - Front Neurosci (2016)

Bottom Line: 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.Besides peripheral toxicological effects, many NPS seem to have addictive properties.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Cagliari Cagliari, Italy.

ABSTRACT
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 Δ(9)-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.

No MeSH data available.


Related in: MedlinePlus

JWH-018 self-administration in rats and mice. (A) JWH-018 self-administration by Sprague-Dawley rats and involvement of CB1 cannabinoid receptors in this behavior. Number of active nose pokes (circles) that resulted in JWH-018 infusion (20 μg/kg/infusion) or inactive ones (triangles) during each 1-h daily session under FR1 and FR 3 during acquisition (1th to 37th sessions), extinction (38th To 47th sessions) and reacquisition (48th to 54thsessions) phases. On sessions 28th and 29th the effect of SR 141716A on the JWH-018 SA was tested. Results are expressed as mean ± SEM (N sessions 10–47 = 14, sessions 48–54 = 6) *p < 0.05 vs. inactive nose pokes; ANOVA followed by LSD post hoc test. (B) JWH-018 self-administration by C57BL/6 mice under fixed (FR1) and progressive (PR) reinforcement schedules. Number of active lever-presses (circles) that resulted in JWH-018 infusion (30 μg/kg/inf) or inactive lever-presses (triangles) during each 2 h daily session under FR1 (9th–15th sessions), and PR (16th session) reinforcement schedules. Results are expressed as mean ± SEM (N = 8), *p < 0.05 vs. inactive lever- presses; ANOVA followed by LSD post hoc test. Adapted from De Luca et al. (2015a).
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Figure 5: JWH-018 self-administration in rats and mice. (A) JWH-018 self-administration by Sprague-Dawley rats and involvement of CB1 cannabinoid receptors in this behavior. Number of active nose pokes (circles) that resulted in JWH-018 infusion (20 μg/kg/infusion) or inactive ones (triangles) during each 1-h daily session under FR1 and FR 3 during acquisition (1th to 37th sessions), extinction (38th To 47th sessions) and reacquisition (48th to 54thsessions) phases. On sessions 28th and 29th the effect of SR 141716A on the JWH-018 SA was tested. Results are expressed as mean ± SEM (N sessions 10–47 = 14, sessions 48–54 = 6) *p < 0.05 vs. inactive nose pokes; ANOVA followed by LSD post hoc test. (B) JWH-018 self-administration by C57BL/6 mice under fixed (FR1) and progressive (PR) reinforcement schedules. Number of active lever-presses (circles) that resulted in JWH-018 infusion (30 μg/kg/inf) or inactive lever-presses (triangles) during each 2 h daily session under FR1 (9th–15th sessions), and PR (16th session) reinforcement schedules. Results are expressed as mean ± SEM (N = 8), *p < 0.05 vs. inactive lever- presses; ANOVA followed by LSD post hoc test. Adapted from De Luca et al. (2015a).

Mentions: This is a review, different authors contributed as follows: CM: Section NPS: From Chemistry to Pharmacological Effects; Figures 1–3, Tables 1, 3, 4. GS and CR: Section–Introduction; MM and MM: Section–Human and Animal Studies on amphetamine-Like Stimulant Effects: Psychoactive Effects, Cognitive Deficits, Emotional Alterations, and Dependence -MM: Table 2. MDL: Section–Synthetic Marijuana and the Cannabimimetics, Section–Concluding Remarks and entire revision of the manuscript; Figures 4, 5 and Tables 3, 4.


Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

Miliano C, Serpelloni G, Rimondo C, Mereu M, Marti M, De Luca MA - Front Neurosci (2016)

JWH-018 self-administration in rats and mice. (A) JWH-018 self-administration by Sprague-Dawley rats and involvement of CB1 cannabinoid receptors in this behavior. Number of active nose pokes (circles) that resulted in JWH-018 infusion (20 μg/kg/infusion) or inactive ones (triangles) during each 1-h daily session under FR1 and FR 3 during acquisition (1th to 37th sessions), extinction (38th To 47th sessions) and reacquisition (48th to 54thsessions) phases. On sessions 28th and 29th the effect of SR 141716A on the JWH-018 SA was tested. Results are expressed as mean ± SEM (N sessions 10–47 = 14, sessions 48–54 = 6) *p < 0.05 vs. inactive nose pokes; ANOVA followed by LSD post hoc test. (B) JWH-018 self-administration by C57BL/6 mice under fixed (FR1) and progressive (PR) reinforcement schedules. Number of active lever-presses (circles) that resulted in JWH-018 infusion (30 μg/kg/inf) or inactive lever-presses (triangles) during each 2 h daily session under FR1 (9th–15th sessions), and PR (16th session) reinforcement schedules. Results are expressed as mean ± SEM (N = 8), *p < 0.05 vs. inactive lever- presses; ANOVA followed by LSD post hoc test. Adapted from De Luca et al. (2015a).
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Related In: Results  -  Collection

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Figure 5: JWH-018 self-administration in rats and mice. (A) JWH-018 self-administration by Sprague-Dawley rats and involvement of CB1 cannabinoid receptors in this behavior. Number of active nose pokes (circles) that resulted in JWH-018 infusion (20 μg/kg/infusion) or inactive ones (triangles) during each 1-h daily session under FR1 and FR 3 during acquisition (1th to 37th sessions), extinction (38th To 47th sessions) and reacquisition (48th to 54thsessions) phases. On sessions 28th and 29th the effect of SR 141716A on the JWH-018 SA was tested. Results are expressed as mean ± SEM (N sessions 10–47 = 14, sessions 48–54 = 6) *p < 0.05 vs. inactive nose pokes; ANOVA followed by LSD post hoc test. (B) JWH-018 self-administration by C57BL/6 mice under fixed (FR1) and progressive (PR) reinforcement schedules. Number of active lever-presses (circles) that resulted in JWH-018 infusion (30 μg/kg/inf) or inactive lever-presses (triangles) during each 2 h daily session under FR1 (9th–15th sessions), and PR (16th session) reinforcement schedules. Results are expressed as mean ± SEM (N = 8), *p < 0.05 vs. inactive lever- presses; ANOVA followed by LSD post hoc test. Adapted from De Luca et al. (2015a).
Mentions: This is a review, different authors contributed as follows: CM: Section NPS: From Chemistry to Pharmacological Effects; Figures 1–3, Tables 1, 3, 4. GS and CR: Section–Introduction; MM and MM: Section–Human and Animal Studies on amphetamine-Like Stimulant Effects: Psychoactive Effects, Cognitive Deficits, Emotional Alterations, and Dependence -MM: Table 2. MDL: Section–Synthetic Marijuana and the Cannabimimetics, Section–Concluding Remarks and entire revision of the manuscript; Figures 4, 5 and Tables 3, 4.

Bottom Line: 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.Besides peripheral toxicological effects, many NPS seem to have addictive properties.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Cagliari Cagliari, Italy.

ABSTRACT
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 Δ(9)-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.

No MeSH data available.


Related in: MedlinePlus