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Delta-9-Tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid and structural analog of THC, exhibits a dual pharmacological profile as a CB1 receptor agonist/antagonist and a partial CB2 agonist. This study evaluated the effects of THCV in a THC discrimination model in rats. Male Sprague-Dawley rats (n = 16, 300–340 g, PND60) were trained under a fixed ratio 20 (FR20) schedule to discriminate THC (3 mg/kg) from vehicle. Substitution tests were conducted with THC (0.325–3 mg/kg), THCV (0.75–6 mg/kg), and THC-THCV combinations. THCV produced an inverted U-shaped substitution curve, significantly differing from vehicle (p = 0.008). At 3 mg/kg, THCV partially substituted for THC (54.6% ± 17.82, p = 0.003). Response rate significantly increased during the substitution test with 3 mg/kg of THCV (p = 0.042). THCV (6 mg/kg) reversed THC (0.75 mg/kg)-induced responding (p = 0.040), with no significant change in response rate (p = 0.247). However, THCV combined with THC (1.5 mg/kg) affected response rates (p = 0.012), with 6 mg/kg significantly reducing rates vs. 3 mg/kg (p = 0.013). Blood THC and 11-OH-THC levels remained unchanged when THC was combined with THCV. The findings suggest THCV can partially mimic or block THC’s discriminative effects in a dose-dependent manner, possibly acting as a partial CB1 agonist.

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of [DELTA]9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1-2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment.

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of [DELTA]9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1-2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment.

The high interest in non-psychoactive cannabidiol increases the need for efficient and straightforward cannabidiol (CBD) extraction methods. The research aimed to compare simple methods of cannabinoid extraction that do not require advanced laboratory equipment. This work assesses the content of total CBD and Δ9-tetrahydrocannabinol (Δ9-THC) in popular solvents such as water and ethanol extracts. Hemp raw material was analyzed with Gas Chromatography with a Flame Ionization Detector (GC-FID), while extracts were tested by High-Performance Liquid Chromatography (HPLC). The female inflorescences of three varieties of industrial hemp were tested: Futura 75, KC Dora, and Tygra (different sowing and N fertilization densities). Tygra (T/10/30) showed the highest content of CBD (0.064%) in water extracts. However, in 80% tincture from Futura 75 (F/30/30), a higher CBD content of 1.393% was observed. The use of 96% ethanol for extraction and ultrasound enabled the highest CBD content to be obtained: 2.682% in Futura 75 (F/30/30). Cold water extraction showed no effect on Δ9-THC content, while hot water extraction increased content from 0.001% in KC Dora to 0.002% in Futura 75 (F/30/30) and Tygra, but the changes were statistically insignificant. Application of 80% ethanol revealed the significantly highest content of Δ9-THC in KC Dora, from 0.026% (K/30/90) to 0.057% (K/30/30), as well as in Tygra (T/30/30) (0.036%) and Futura 75 (F/30/30) (0.048%). The use of ethanol extraction in combination with ultrasound could be an efficient method of obtaining cannabinoids.

• Demand for cannabidiol (CBD), the predominant cannabinoid in hemp (Cannabis sativa), has favored cultivars producing unprecedented quantities of CBD. We investigated the ancestry of a new cultivar and cannabinoid synthase genes in relation to cannabinoid inheritance. • A nanopore-based assembly anchored to a high-resolution linkage map provided a chromosome-resolved genome for CBDRx, a potent CBD-type cultivar. We measured cannabinoid synthase expression by cDNA sequencing and conducted a population genetic analysis of diverse Cannabis accessions. Quantitative trait locus mapping of cannabinoids in a hemp × marijuana segregating population was also performed. • Cannabinoid synthase paralogs are arranged in tandem arrays embedded in long terminal repeat retrotransposons on chromosome 7. Although CBDRx is predominantly of marijuana ancestry, the genome has cannabidiolic acid synthase (CBDAS) introgressed from hemp and lacks a complete sequence for tetrahydrocannabinolic acid synthase (THCAS). Three additional genomes, including one with complete THCAS, confirmed this genomic structure. Only cannabidiolic acid synthase (CBDAS) was expressed in CBD-type Cannabis, while both CBDAS and THCAS were expressed in a cultivar with an intermediate tetrahydrocannabinol (THC) : CBD ratio. • Although variation among cannabinoid synthase loci might affect the THC : CBD ratio, variability among cultivars in overall cannabinoid content (potency) was also associated with other chromosomes.

The effects of Δ[sup.9]-tetrahydrocannabinol (THC) on adipocyte function under obesogenic, free-fatty-acid (FFA)-rich conditions remain poorly characterized, particularly regarding adipogenesis, FFA buffering, and downstream hepatocyte lipid handling. We investigated THC’s effect on adipogenic differentiation, temporal FFA buffering in mature adipocytes under lipid stress, and hepatocyte lipid accumulation driven by extracellular FFAs. The 3T3-L1 preadipocytes were differentiated in 0.5 mM oleate: palmitate (2:1) medium with vehicle (EtOH), THC (1 μM), or rosiglitazone (30 μM). Adipogenesis was assessed using BODIPY/NucSpot 650 staining followed by lipid droplet (LD) analysis. Adipocytes (days 10–18) were monitored for lipid accumulation, LD morphology, lipolysis, extracellular non-esterified fatty acids (NEFA), and lipid-handling gene expression. Conditioned media (CM) were applied to AML12 hepatocytes to assess lipid uptake. By day 6, THC enhanced adipogenesis, increasing lipid accumulation. In mature adipocytes, THC induced a biphasic buffering response: on day 10, NEFA levels were elevated despite unchanged lipid content, with increased isoproterenol-stimulated lipolysis. By day 18, buffering improved, with enhanced lipid storage, elevated stimulated lipolysis, smaller LDs, and altered gene expression. AML12 lipid accumulation corresponded with residual NEFA in CM, indicating that adipocyte FFA sequestration modulates hepatocyte lipid uptake. These findings reveal that under FFA-rich conditions, THC promotes late-stage adipogenesis and remodels adipocyte lipid handling, regulating extracellular FFA availability and hepatocyte lipid loading.

Introduction The use of cannabis as a sleep aid has increased despite inadequate evidence of its efficacy or associated risks. Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive constituent of cannabis. Acute THC administration can induce CB1R mediated reductions in total peripheral resistance resulting in dose-dependent increases in heart rate and reductions in heart rate variability (HRV) in awake subjects. However, the influence of THC on vagal-cardiac modulation during sleep is unclear. Methods 7 individuals who use cannabis (>3x/week for 3 months; CUDIT-R = 8±1) and 8 cannabis-naïve participants (combined: age range 21-32 years; 9 female) were recruited to participate in this repeated measure, single blinded, placebo-controlled study. One hour before habitual sleep, participants received either a placebo pill or 10mg of THC. Polysomnography (PSG) and ECG were recorded over these 2 nights. HRV was assessed in both time and frequency domains in 2-min epochs of stable N2, N3 and REM sleep. Repeated measures ANOVA comparisons were made for PSG and HRV variables. [(*)=p< 0.05] Results There were no significant changes in total sleep duration or sleep architecture (N2%, N3%, & REM%) between the placebo and dosing night in either group. Compared to the placebo night, both individuals who use cannabis and cannabis naïve participants exhibited significant decreases in HRV variables throughout the night when dosed with THC. R-R interval decreased by 25±10* ms [mean±SE] (2%) in the naïve group and 62±11* ms (6%) in the cannabis group. RMSSD decreased by 15±3* ms (22%) in the naïve group and 11±3* ms (23%) in the cannabis group. PNN50 decreased by 9±3* % in the naïve group and 11±3* % in the cannabis group. In naïve participants high frequency spectral power decreased by 398±76* ms^2 (32%). Conclusion Our results suggest that THC ingestion before bedtime did not systematically affect sleep depth or duration, but did significantly reduce vagal-cardiac modulation in individuals who use cannabis as well as in cannabis naïve participants. Acute reductions in parasympathetic control of the heart may indicate increased cardiovascular stress during sleep when THC is ingested. Support (if any) AASM; K01HL151745; T32HL083808; OHSU OFDIR; R35 HL155681; Oregon Institute of Occupational Health Sciences