The potential utility of some legal highs in CNS disorders

Davidson, Charles S.; Schifano, Fabrizio

doi:10.1016/j.pnpbp.2015.07.010

Cited by 12 publications

(5 citation statements)

References 150 publications

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“…Given DPH is also an antagonist at NMDA receptors, as well as a DAT blocker, it may even have potential as a fast-acting antidepressant as seen with ketamine [ 61 ]. We have previously reviewed the potential use of novel psychoactive substances, including dissociatives, such as DPH, in CNS disorders [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines

et al. 2018

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Novel psychoactive substances (NPS) may have unsuspected addiction potential through possessing stimulant properties. Stimulants normally act at the dopamine transporter (DAT) and thus increase dopamine (DA) availability in the brain, including nucleus accumbens, within the reward and addiction pathway. This paper aims to assess DAT responses to dissociative diarylethylamine NPS by means of in vitro and in silico approaches. We compared diphenidine (DPH) and 2-methoxydiphenidine (methoxphenidine, 2-MXP/MXP) for their binding to rat DAT, using autoradiography assessment of [125I]RTI-121 displacement in rat striatal sections. The drugs’ effects on electrically-evoked DA efflux were measured by means of fast cyclic voltammetry in rat accumbens slices. Computational modeling, molecular dynamics and alchemical free energy simulations were used to analyse the atomistic changes within DAT in response to each of the five dissociatives: DPH, 2-MXP, 3-MXP, 4-MXP and 2-Cl-DPH, and to calculate their relative binding free energy. DPH increased DA efflux as a result of its binding to DAT, whereas MXP had no significant effect on either DAT binding or evoked DA efflux. Our computational findings corroborate the above and explain the conformational responses and atomistic processes within DAT during its interactions with the dissociative NPS. We suggest DPH can have addictive liability, unlike MXP, despite the chemical similarities of these two NPS.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines

et al. 2018

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“…Moreover, attempts towards potential therapeutic applications of NPS, moving from their pharmacological properties, have been recently made (Davidson & Schifano, ). However, at present, these hypotheses are merely speculative and they are not specifically addressed in this paper.…”

Section: Discussionmentioning

confidence: 99%

Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter‐observational study

Acciavatti

Lupi

Santacroce

et al. 2017

Human Psychopharmacology

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“…The sum of these effects on emotional regulation, together with the decrease of anger observed in the POMS, could make 2C-B a potentially useful psychotherapeutic tool to treat changes of attitude in disorders related to violence and aggression through affective reevaluation. At present there is heated debate regarding the therapeutic potential of psychedelic drugs and their legal reclassification in order to investigate their potential use as medication [ 86 , 87 ]. In a similar fashion to other NPS, 2C-B is widely available online to anyone (including adolescents and vulnerable individuals), and the risks of falsification and adulterants must be considered.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

González

Torrens

Farré

2015

BioMed Research International

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Background. 2C-B (Nexus) is one of the most widespread novel psychoactive substances. There is limited information about its pharmacological properties, and few studies in humans concern its acute and chronic effects. 2C-B has been classified as a stimulant, hallucinogen, entactogen, and/or empathogen. Objectives. To evaluate the emotional, subjective, and cardiovascular effects of 2C-B. Methods. Twenty healthy recreational 2C-B users (12 women) self-administered a 20 mg dose of 2C-B. Evaluations included emotional (IAPS, FERT, and speech), subjective (visual analog scales, ARCI, VESSPA, HRS, and POMS questionnaires), and cardiovascular effects (blood pressure and heart rate). Results. Positive subjective effects predominated with a reduction of anger under the influence of 2C-B. It did, however, increase reactivity to negative emotional stimuli and decrease the ability to recognize expressions of happiness. Augmented emotionality in speech could be appreciated by others. 2C-B induced euphoria and well-being, changes in perceptions, and slight hallucinogenic states. Mild sympathetic actions were observed. Conclusions. The specific profile that 2C-B exerts on emotions suggests its classification as an entactogen with psychedelic properties.

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The potential utility of some legal highs in CNS disorders

Cited by 12 publications

References 150 publications

Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines

Mechanistic Insights into the Stimulant Properties of Novel Psychoactive Substances (NPS) and Their Discrimination by the Dopamine Transporter—In Silico and In Vitro Exploration of Dissociative Diarylethylamines

Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter‐observational study

Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions

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