Methamphetamine (METH) is a potent psychostimulant with neurotoxic properties. Heavy use increases the activation of neuronal nitric oxide synthase (nNOS), production of peroxynitrites, microglia stimulation, and induces hyperthermia and anorectic effects. Most METH recreational users also consume cannabis. Preclinical studies have shown that natural (D9- tetrahydrocannabinol, D9-THC) and synthetic cannabinoid CB1 and CB2 receptor agonists exert neuroprotective effects on different models of cerebral damage. Here, we investigated the neuroprotective effect of D9-THC on METH-induced neurotoxicity by examining its ability to reduce astrocyte activation and nNOS overexpression in selected brain areas. Rats exposed to a METH neurotoxic regimen (4610 mg/kg, 2 hours apart) were pre-...

Rationale: Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects. Objectives: The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity. Methods: In an open-label pilot study, six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances—five patients with Alzheimer’s disease and one patient with vascular dementia—were treated with 2.5 mg dronabinol daily for 2 weeks. Motor activity was measured objectively using actigraphy. Results: Compared to baseline, dronabinol led to...

Plant-derived cannabinoids, including #9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells, although the precise mechanism remains unclear. In the current study, we investigated the effect of THC on the upstream and downstream events that modulate the extracellular signal-regulated kinase (ERK) module of mitogen-activated protein kinase pathways primarily in human Jurkat leukemia T cells. The data showed that THC down-regulated Raf-1/mitogenactivated protein kinase/ERK kinase (MEK)/ERK/RSK pathway leading to translocation of Bad to mitochondria. THC also decreased the phosphorylation of Akt. However, no significant association of Bad translocation with phosphatidylinositol 3-kinase/Akt and protein kinase A signaling pathways was noted when treated cells were examined in relation to...

9 -Tetrahydrocannabinol (THC), the main psychoactive component of marijuana has been shown to suppress the immune response. However, the exact mechanism of THC-induced immunosuppression remains unclear. In the current study, we tested the hypothesis that exposure to THC leads to the induction of apoptosis in lymphocyte populations. Splenocytes of C57BL/6 mice cultured in the presence of 10 M or greater concentrations of THC showed significantly reduced proliferative response to mitogens, including anti-CD3 monoclonal antibodies (mAbs), concanavalin A (Con A), and lipopolysaccharide (LPS) in vitro. Thymocytes and naive and activated splenocytes exposed to 10 M or 20 M THC showed significantly increased levels of apoptosis....

Aim: Cannabinoids (CB) like Δ 16 9 -tetrahydrocannabinol (THC) can induce cancer cell apoptosis and inhibit angiogenesis. However, the use of cannabinoids for the treatment of malignant diseases is discussed 17 controversially because of their immunomodulatory effects which can suppress anti-tumor immunity. Here 18 we investigated the role of exogenous and endogenous cannabinoids in mouse skin cancer. 19 Main methods: First we examined the effect of THC, which binds to CB receptors (CB1, CB2), on the growth of the 20 mouse melanoma cell lines B16 and HCmel12 in vitro and in vivo in wild type (WT) and CB1/CB2-receptor 21 deficient mice (Cnr1/2 22 −/−)....

Chronic treatment with Δ 9 -tetrahydrocannabinol (THC) produces tolerance to cannabinoid-mediated behaviors and region-specific adaptation of brain cannabinoid receptors. However, the relationship between receptor adaptation and tolerance is not well understood, and the dose-response relationship of THC-induced cannabinoid receptor adaptation is unknown. This study assessed cannabinoid receptor function in the brain and cannabinoid-mediated behaviors after chronic treatment with different dosing regimens of THC. Mice were treated twice per day for 6.5 days with the following: vehicle, 10 mg/kg THC, or escalating doses of 10 to 20 to 30 or 10 to 30 to 60 mg/kg THC. Tolerance to cannabinoid-mediated locomotor inhibition, ring immobility, antinociception,...

Rationale: No studies to date have directly compared the tolerability and efficacy of smoked marijuana and oral dronabinol in HIV+ marijuana smokers. Objectives: The aim of this study was to compare dronabinol (0, 10, 20, 30 mg p.o.) and marijuana [0.0, 1.8, 2.8, 3.9% Δ9 -tetrahydrocannabinol (THC)] in two samples of HIV+ marijuana smokers: those with (n=15) and those without (n=15) a clinically significant loss of muscle mass (<90% body cell mass/height), which is one component of AIDS wasting. Methods: Mood, physical symptoms, self-selected food intake, cardiovascular data, and cognitive task performance were measured before and repeatedly after dronabinol and marijuana administration in eight...

Background: It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia. Methods: To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry. CB-receptor antagonists as well as a CRISPR double nickase knockdown approach were used to evaluate for receptor specificity of the observed proapoptotic...

1. Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30-32' C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4-fold at 500 mg/kg. 2. Under these conditions, ether sleeping time was not prolonged. 3. Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome-rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation. 4. A'-Tetrahydrocannabinol (A'-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water-soluble fractions of...

The effects of cannabis extracts on nocturnal sleep, earlymorning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg D-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 PM. The electroencephalogram was recorded during the sleep period (11 PM to 7 AM). Performance, sleep latency, and...