Plasma and Brain Levels of Δ<sup>6</sup>‐THC and Seven Monooxygenated Metabolites Correlated to the Cataleptic Effect in the Mouse

Ohlsson, A; Widman, M; Carlsson, Stefan; Ryman, Torsten; Strid, C

doi:10.1111/j.1600-0773.1980.tb03660.x

Cited by 29 publications

(1 citation statement)

References 25 publications

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“…Most acute studies using THC employ an oral or inhalation route of administration [77]. Oral administration delays the onset of effects by 30 min to two hours, produces lower peak plasma levels, and prolongs the action of the THC compared to the inhaled or intravenous route [88,89].…”

Section: Data Synthesismentioning

confidence: 99%

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

et al. 2020

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Background Cannabis has been documented for use in alleviating anxiety. However, certain research has also shown that it can produce feelings of anxiety, panic, paranoia and psychosis. In humans, Δ9-tetrahydrocannabinol (THC) has been associated with an anxiogenic response, while anxiolytic activity has been attributed mainly to cannabidiol (CBD). In animal studies, the effects of THC are highly dose-dependent, and biphasic effects of cannabinoids on anxiety-related responses have been extensively documented. A more precise assessment is required of both the anxiolytic and anxiogenic potentials of phytocannabinoids, with an aim towards the development of the ‘holy grail’ in cannabis research, a medicinally-active formulation which may assist in the treatment of anxiety or mood disorders without eliciting any anxiogenic effects. Objectives To systematically review studies assessing cannabinoid interventions (e.g. THC or CBD or whole cannabis interventions) both in animals and humans, as well as recent epidemiological studies reporting on anxiolytic or anxiogenic effects from cannabis consumption. Method The articles selected for this review were identified up to January 2020 through searches in the electronic databases OVID MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Results Acute doses of CBD were found to reduce anxiety both in animals and humans, without having an anxiogenic effect at higher doses. Epidemiological studies tend to support an anxiolytic effect from the consumption of either CBD or THC, as well as whole plant cannabis. Conversely, the available human clinical studies demonstrate a common anxiogenic response to THC (especially at higher doses). Conclusion Based on current data, cannabinoid therapies (containing primarily CBD) may provide a more suitable treatment for people with pre-existing anxiety or as a potential adjunctive role in managing anxiety or stress-related disorders. However, further research is needed to explore other cannabinoids and phytochemical constituents present in cannabis (e.g. terpenes) as anxiolytic interventions. Future clinical trials involving patients with anxiety disorders are warranted due to the small number of available human studies.

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Section: Data Synthesismentioning

confidence: 99%

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

et al. 2020

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Do Plasma Concentrations of Δ⁹‐Tetrahydrocannabinol Reflect the Degree of Intoxication?

Hollister

Gillespie

Ohlsson

et al. 1981

The Journal of Clinical Pharma

149

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Plasma concentrations of THC were measured by gas‐liquid chromatography and mass spectrometry following three routes of administration and correlated with clinical effects. Plasma concentrations peaked at 3 minutes after intravenous injection and then sharply declined. The peak “high” occurred at 30 minutes while plasma concentrations were declining. This lag between plasma concentration and “high” continued during most of the span of the drug's effects. The situation was quite similar following smoking, except that peak plasma concentrations were lower. After oral administration of THC, absorption was slow, with peak concentration occurring at 1 to 2 hours. Plasma concentrations were much lower. Correlations between plasma concentrations of drug and “high” were significant but not impressive. The degree of “high” was quite variable in relation to the prevailing plasma concentration. Conjunctival injection was found so long as plasma concentration of THC could be measured. Pulse rate increases occurred at lower concentration after oral administration than after the other two routes. It is unlikely that a range of plasma concentrations can be reliably equated with impaired performance. The mode of administration will become important should THC or some homolog become a therapeutic agent.

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A search for properties which produce discrimination between cannabinoid psychoactivity and analgesic activity

Reggio

1992

Int J of Quantum Chemistry

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One long-range goal of our work has been the design of cannabinoid analgesics with reduced psychopharmacological liability. We review here the progress we have made toward this goal. When we began our work on the cannabinoids, no cannabinoid analgesic had been reported that did not also possess significant psychoactivity. We approached the cannabinoid problem by calculating molecular reactivity characteristics (MRCS) of template molecules for each activity: (-)-trans-delta-9-tetrahydrocannabinol (A'-THC) for psychoactivity, and (-)-9-nor-9-betahydroxyhexahydrocannabinol (9-nor-9p-OH-HHC) for analgesic activity. We then compared the MRCS of each template with the MRCS of a carefully chosen set of other cannabinoids (both active and inactive). Our focus in the calculation of MRCS was on accessible conformations of each subject molecule and on the molecular electrostatic potential generated in key planes by each accessible conformer. Our working hypothesis concerning the molecular basis of psychopharmacological activity in the cannabinoids was that activity is conferred by the set of molecular properties generated (1) by the orientation of the lone pairs of electrons of the phenyl group hydroxyl oxygen and (2) by the orientation of the carbocyclic ring and its C-9 substituent relative to this oxygen. Our working hypothesis concerning the molecular basis of cannabinoid analgesic activity was that activity is conferred by the set of molecular properties generated by the presence and relative location of two negative potential regions in the top half of the cannabinoid analgesic molecule. Our work thus far has revealed important steric and electronic features of the cannabinoids that may be used to enhance discrimination. We have shown that a simple structural feature, a C-9 substituent protruding into the a face of the molecule, can abolish or significantly diminish psychoactivity. We have also demonstrated that a free phenol group is not an absolute requirement for activity. Instead, we have found that compounds that do not possess free phenolic hydrogens, but that do maintain the orientation of the lone pairs of electrons of the "phenolic" oxygen toward the carbocyclic ring, exhibit selectivity toward analgesia.

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Plasma and Brain Levels of Δ⁶‐THC and Seven Monooxygenated Metabolites Correlated to the Cataleptic Effect in the Mouse

Cited by 29 publications

References 25 publications

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Do Plasma Concentrations of Δ⁹‐Tetrahydrocannabinol Reflect the Degree of Intoxication?

A search for properties which produce discrimination between cannabinoid psychoactivity and analgesic activity

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Plasma and Brain Levels of Δ6‐THC and Seven Monooxygenated Metabolites Correlated to the Cataleptic Effect in the Mouse

Cited by 29 publications

References 25 publications

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties

Do Plasma Concentrations of Δ9‐Tetrahydrocannabinol Reflect the Degree of Intoxication?

A search for properties which produce discrimination between cannabinoid psychoactivity and analgesic activity

Contact Info

Product

Resources

About

Plasma and Brain Levels of Δ⁶‐THC and Seven Monooxygenated Metabolites Correlated to the Cataleptic Effect in the Mouse

Do Plasma Concentrations of Δ⁹‐Tetrahydrocannabinol Reflect the Degree of Intoxication?