Herbal Highs: Review on Psychoactive Effects and Neuropharmacology

Cannabidiol (CBD), a lipophilic cannabinoid compound without psychoactive effects, has emerged as adjuvant of anti-epileptic drugs (AEDs) in the treatment of refractory epilepsy (RE), decreasing the severity and/or frequency of seizures. CBD is considered a multitarget drug that could act throughout the canonical endocannabinoid receptors (CB1-CB2) or multiple non-canonical pathways. Despite the fact that the CBD mechanism in RE is still unknown, experiments carried out in our laboratory showed that CBD has an inhibitory role on P-glycoprotein excretory function, highly related to RE. Since CB2 is expressed mainly in the immune cells, we hypothesized that CBD treatment could alter the activity of polymorphonuclear neutrophils (PMNs) in a similar way that it does with microglia/macrophages and others circulating leukocytes. In vitro, CBD induced PMN cytoplasmatic vacuolization and proapoptotic nuclear condensation, associated with a significantly decreased viability in a concentration-dependent manner, while low CBD concentration decreased PMN viability in a time-dependent manner. At a functional level, CBD reduced the chemotaxis and oxygen consumption of PMNs related with superoxide anion production, while the singlet oxygen level was increased suggesting oxidative stress damage. These results are in line with the well-known CBD anti-inflammatory effect and support a potential immunosuppressor role on PMNs that could promote an eventual defenseless state during chronic treatment with CBD in RE.

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CB cannabinoid receptor agonists: pain relief without psychoactive effects?

Current Opinion in Pharmacology ◽

10.1016/s1471-4892(02)00004-8 ◽

2003 ◽

Vol 3 (1) ◽

pp. 62-67 ◽

Cited By ~ 140

Author(s):

T MALANJR ◽

M IBRAHIM ◽

J LAI ◽

T VANDERAH ◽

A MAKRIYANNIS ◽

...

Keyword(s):

Pain Relief ◽

Cannabinoid Receptor ◽

Receptor Agonists ◽

Psychoactive Effects

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An Introduction to Cannabis

Cannabinoids and the Brain ◽

10.7551/mitpress/9780262035798.003.0001 ◽

2017 ◽

Author(s):

Linda A. Parker

Keyword(s):

Therapeutic Potential ◽

Scientific Investigation ◽

Human History ◽

Preclinical Research ◽

Cannabinoid Compounds ◽

Psychoactive Effects ◽

The Brain

Although cannabis has been used throughout human history, the scientific investigation of its effects only began with the isolation of THC in the 1960’s. Once discovered it was another 20 years before the mechanism by which THC produces its psychoactive effects in the brain, the CB1 receptor, was discovered. Cannabis contains over 80 cannabinoid compounds, but THC is the only intoxicating compound. Recent preclinical research is being directed towards evaluating the therapeutic potential of other cannabinoid compounds found in cannabis, including CBD. The pharmacokinetics of THC, methods of administration, and dosing issues are explored in Chapter 1.

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PHARMACOLOGY OF NOVAL CANNABINOIDS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2020v12i1.36005 ◽

2019 ◽

pp. 1-5

Author(s):

SUMITHA S. K. ◽

VEENA S. PATTAMMADY ◽

R. SAMBATHKUMAR

Keyword(s):

Cannabis Sativa ◽

Synthetic Cannabinoids ◽

Systemic Circulation ◽

Scientific Investigation ◽

Direct Relation ◽

Preclinical Research ◽

First Pass Metabolism ◽

First Pass ◽

Psychoactive Effects ◽

Pass Metabolism

Cannabis is a plant rich in various compounds that have a variety of impacts on the physiology of humans and the effects of these metabolites have a significant role in managing a variety of clinical diseases. A substantial increase in the use of SC (synthetic cannabinoids) had seen in the last few years especially infrequent cannabis users. The SCs will generate psychoactive effects that were similar to cannabis. However, the composition and pharmacological characteristics of these drugs make them possibly hazardous. Like all drugs, cannabis’ pharmacokinetics depends on the route of administration. Several studies showed that the bioavailability is less in oral administration when compared to inhalation. The main reason for this decrease in oral bioavailability is that cannabinoids undergo the first-pass metabolism before entering into the systemic circulation whereas in inhalation, it enters the circulation directly through the lungs. Cannabis sativa is a psychoactive plant that contains more than 500 components of which 104 cannabinoids had been identified. Of these, 2 components such as Δ9-THC (Δ9-tetrahydrocannabinol) and CBD (cannabidol) were under the scientific investigation. Δ9-THC is the primary cannabinoid which was responsible for the consequences of psychotrophy. The potency of cannabis is assessed based on the THC concentration of a sample that is the main psychoactive cannabinoid in cannabis. The adverse effects are in direct relation to the concentration of THC in the product after regular cannabis use. It can be assumed that several cannabinoids will find their way into the pharmacies from preclinical research within a century.

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Development of legal highs

Journal of Psychiatric Intensive Care ◽

10.1017/s1742646415000011 ◽

2015 ◽

Vol 11 (02) ◽

pp. 128-137 ◽

Cited By ~ 1

Author(s):

Brenda Wasunna ◽

Emily Thomas ◽

Sally Morgan

Keyword(s):

Mental Health ◽

Health Effect ◽

Psychiatric Services ◽

Drug Control ◽

New Psychoactive Substances ◽

Psychoactive Substances ◽

Legal Highs ◽

Controlled Drugs ◽

Research Chemicals ◽

Herbal Highs

AbstractNew psychoactive substances (NPS) or ‘legal highs’ are defined as unregulated psychoactive substances including synthetic and/or plant derived substances (marketed as research chemicals, party pills and herbal highs) that are intended to mimic the effects of controlled drugs. Psychiatric services around the country are seeing a rise in the use of NPS complicating mental health presentations. The challenge surrounding these substances is the fact that they are not under the international drug control system and are proving to have a detrimental health effect on users. This article reviews the current literature on this subject and discusses some of the most common examples of NPS and their potential effects on mental health.

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Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa087 ◽

2020 ◽

Cited By ~ 1

Author(s):

Bashkim Kadriu ◽

Maximillian Greenwald ◽

Ioline D Henter ◽

Jessica R Gilbert ◽

Christoph Kraus ◽

...

Keyword(s):

Therapeutic Response ◽

Network Activity ◽

Dependent Manner ◽

Network Efficiency ◽

Rigorous Research ◽

Antidepressant Effects ◽

Psychoactive Effects ◽

Antidepressant Efficacy ◽

Molecular Effects ◽

Activity Dependent

Abstract Background The glutamatergic modulator ketamine has created a blueprint for studying novel pharmaceuticals in the field. Recent studies suggest that “classic” serotonergic psychedelics (SPs) may also have antidepressant efficacy. Both ketamine and SPs appear to produce rapid, sustained antidepressant effects after a transient psychoactive period. Methods This review summarizes areas of overlap between SP and ketamine research and considers the possibility of a common, downstream mechanism of action. The therapeutic relevance of the psychoactive state, overlapping cellular and molecular effects, and overlapping electrophysiological and neuroimaging observations are all reviewed. Results Taken together, the evidence suggests a potentially shared mechanism wherein both ketamine and SPs may engender rapid neuroplastic effects in a glutamatergic activity-dependent manner. It is postulated that, though distinct, both ketamine and SPs appear to produce acute alterations in cortical network activity that may initially produce psychoactive effects and later produce milder, sustained changes in network efficiency associated with therapeutic response. However, despite some commonalities between the psychoactive component of these pharmacologically distinct therapies—such as engagement of the downstream glutamatergic pathway—the connection between psychoactive impact and antidepressant efficacy remains unclear and requires more rigorous research. Conclusions Rapid-acting antidepressants currently under investigation may share some downstream pharmacological effects, suggesting that their antidepressant effects may come about via related mechanisms. Given the prototypic nature of ketamine research and recent progress in this area, this platform could be used to investigate entirely new classes of antidepressants with rapid and robust actions.

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A Neglected Link Between the Psychoactive Effects of Dietary Ingredients and Consciousness-Altering Drugs

Frontiers in Psychiatry ◽

10.3389/fpsyt.2019.00591 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Neil R. Smalheiser

Keyword(s):

Psychoactive Effects

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Toward the identification of a phytocannabinoid-like compound in the flowers of a South African medicinal plant (Leonotis leonurus)

BMC Research Notes ◽

10.1186/s13104-020-05372-z ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

E. Hunter ◽

M. Stander ◽

J. Kossmann ◽

S. Chakraborty ◽

S. Prince ◽

...

Keyword(s):

South African ◽

High Performance ◽

Bioactive Compound ◽

Global Trends ◽

Psychoactive Effects ◽

History Of ◽

History Of Use ◽

Therapeutic Compounds ◽

Layer Chromatography ◽

Leonotis Leonurus

Abstract Objective Current global trends on natural therapeutics suggest an increasing market interest toward the use and discovery of new plant-derived therapeutic compounds, often referred to as traditional medicine (TM). The Cannabis industry is currently one such focal area receiving attention, owing to the occurrence of phytocannabinoids (pCBs) which have shown promise in health-promotion and disease prevention. However, the occurrence of pCBs in other plant species are often overlooked and rarely studied. Leonotis leonurus (L.) R. Br. is endemic to South Africa with a rich history of use in TM practices amongst indigenous people and, has been recorded to induce mild psychoactive effects akin to Cannabis. While the leaves have been well-reported to contain therapeutic phytochemicals, little information exists on the flowers. Consequently, as part of a larger research venture, we targeted the flowers of L. leonurus for the identification of potential pCB or pCB-like compounds. Results Flower extracts were separated and analyzed using high performance thin layer chromatography (HPTLC). A single pCB candidate was isolated from HPTLC plates and, using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS), we could successfully group this compound as a fatty amide and tentatively identified as 7,10,13,16-Docosatetraenoylethanolamine (adrenoyl-EA), a known bioactive compound.

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