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Contains fulltext : 291652.pdf (Publisher’s version ) (Open Access) BACKGROUND: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ(9)-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined. METHODS: In this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco(2) of 55 mm Hg or 7.3 kPa (V(E)55), measured at 1-h intervals for 7 h after placebo/oxycodone intake. RESULTS: In 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in V(E)55, whereas placebo was without effect on V(E)55. The first cannabis inhalation resulted in V(E)55 changing from 20.3 (3.1) to 23.8 (2.4) L min(-1) (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min(-1) (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on V(E)55, but slightly increased sedation. CONCLUSIONS: In humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment. CLINICAL TRIAL REGISTRATION: 2021-000083-29 (EU Clinical Trials Register.). 2A p.

Supplemental Digital Content is Available in the Text. This experimental highly controlled trial in 20 patients with fibromyalgia shows that the cannabinoid THC, but not CBD, is effective in the treatment of fibromyalgia pain., In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in 20 chronic pain patients with fibromyalgia. We tested 4 different cannabis varieties with exact knowledge on their ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) content: Bedrocan (22.4-mg THC

Cannabis has been suggested to impair the capacity to recognize discrepancies between expected and executed actions. However, there is a lack of conclusive evidence regarding the acute impact of cannabis on the neural correlates of error monitoring. In order to contribute to the available knowledge, we used a randomized, double-blind, between-groups design to investigate the impact of administration of a low (5.5 mg THC) or high (22 mg THC) dose of vaporized cannabis vs. placebo on the amplitudes of the error-related negativity (ERN) and error positivity (Pe) in the context of the Flanker task, in a group of frequent cannabis users (required to use cannabis minimally 4 times a week, for at least 2 years). Subjects in the high dose group (n=18) demonstrated a significantly diminished ERN in comparison to the placebo condition (n=19), whereas a reduced Pe amplitude was observed in both the high and low dose (n=18) conditions, as compared to placebo. The results suggest that a high dose of cannabis may affect the neural correlates of both the conscious (late), as well as the initial automatic processes involved in error monitoring, while a low dose of cannabis might impact only the conscious (late) processing of errors.

In sum, existing research seems to undermine Schier's et al. (2012) suggestion regarding the lack of a relationship between CBD and cognition. Rather, it seems that both cognitive and affective consequences of CBD administration may be mediated by the ACC. However, the lack of clear-cut results renders the extent and nature of this modulation unclear. The diversity of findings may be explained by various factors, including differential activation of the cognitive and affective subdivisions of the ACC (Bush et al., 2000), the slow onset of action and inconsistent bioavailability of orally administered cannabinoids (Hazekamp et al., 2006), the dosage of CBD (Marco et al., 2011), or whether CBD was administered alone, or in combination with THC (Pertwee, 2008). Furthermore, since modulation of the cognitive effects of cannabinoids has been linked to polymorphism of the cannabinoid receptor (CNR1) gene (Beng-Choon et al., 2011; Stadelman et al., 2011), it is possible that some genetic predispositions of the studied samples could have influenced the results. From this perspective, also the catechol-O-methyltransferase (COMT) gene seems to be a plausible moderating factor due to its role in cognitive control (Colzato et al., 2010) and the pharmacological interactions between the endocannabinoid and dopamine systems (Fattore et al., 2010). In any case, inclusion of new variables could further clarify the CBD–ACC relationship and its role in the aspects of conflict monitoring and emotional processing.

Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR), a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.