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  • D9-Tetrahydrocannabinol (THC), Pulmonary Function
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Bronchodilator Effect of Delta-Tetrahydrocannabinol

The principal psycho-active constituent of cannabis, ∆-trans-tetrahydrocannabinol (∆-THC) has bronchodilator activity in man, both in normal subjects (Vachon, Fitzgerald, Solliday, Gould & Gaensler, 1973; Tashkin, Shapiro & Frank, 1973) and in asthmatic patients (Tashkin, Shapiro & Frank, 1974). It may be given orally, but in order to achieve significant effects, doses in excess of 10 mg must be used and patients then experience psychic disturbance. A dose of 200 ug, is an effective bronchodilator when delivered by inhalation from a pressurized aerosol, and no measurable systemic absorption takes place (Williams, Hartley & Graham, 1976). Higher doses frequently cause transient coughing and chest discomfort in...
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Hemp Oil Ingestion Causes Positive Urine Tests for Ag-Tetrahydrocannabinol Carboxylic Acid

A hemp oil product (Hemp Liquid Gold TM) was purchased from a specialty food store. Fifteen milliliters was consumed by seven adult volunteers. Urine samples were taken from the subjects before ingestion and at 8, 24, and 48 h after the dose was taken. All specimens were screened by enzyme immunoassay with SYVA EMIT II THC 20, THC 50, and THC 100 kits. The tetrahydrocannabinol carboxylic acid (THCA) concentration was determined on all samples by gas chromatography-mass spectrometry (GC-MS) (5). A total of 18 postingestion samples were submitted. Fourteen of the samples screened above the 20-ng cutoff, seven were above the 50-ng cutoff, and...
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Histone Modifications Are Associated with Delta (9)-tetrahydrocannabinol-Mediated Alterations in Antigen-Specific T Cell Responses

Marijuana is one of the most abused drugs due to its psychotropic effects. Interestingly, it is also used for medicinal purposes. The main psychotropic component in marijuana, Δ 9 - tetrahydrocannabinol (THC), has also been shown to mediate potent anti-inflammatory properties. Whether the immunomodulatory activity of THC is mediated by epigenetic regulation has not been investigated previously. In this study, we employed ChIP-Seq technology to examine the in vivo effect of THC on global histone methylation in lymph node cells of mice immunized with a superantigen, staphylococcal enterotoxin B (SEB). We compared genome-wide histone H3K4, H3K27, H3K9, H3K36 trimethylation and H3K9 acetylation patterns in...
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A pilot clinical study of D9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

D9 -Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC...
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Influence of Treatment of Tourette Syndrome with D9-Tetrahydrocannabinol (D9-THC) on Neuropsychological Performance

Previous studies have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (D9-THC), the major psychoactive ingredient of marijuana, are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users, we performed a randomized double-blind placebocontrolled crossover trial for D9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of D9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance. Using a variety of neuropsychological tests, we found no significant differences after treatment with D9-THC compared to placebo...
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A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol

This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as anti-inflammatory substances independent of cyclo-oxygenase (COX) inhibition. CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety...
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Long ­term behavioral and biochemical effects of an ultra-­low dose of Δ9 ­ tetrahydrocannabinol (THC): neuroprotection and ERK signaling

We have previously reported that a single injection of an ultra-low dose of delta-9-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) protected the brain from pentylenentetrazole (PTZ)-induced cognitive deficits when applied 1–7 days before or 1–3 days after the insult. In the present study we expanded the protective profile of THC by showing that it protected mice from cognitive deficits that were induced by a variety of other neuronal insults, including pentobarbital-induced deep anesthesia, repeated treatment with 3,4 methylenedioxymethamphetamine (MDMA; “ecstasy”) and exposure to carbon monoxide. The protective effect of THC lasted for at least 7 weeks. The same ultra-low dose of THC (0.002 mg/kg,...
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Activity of cannabis in relation to its delta’-trans-tetrahydro-cannabinol content

Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than...
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Marijuana, Tetrahydrocannabinol, and Pulmonary Antibacterial Defenses

Although marijuana is now consumed extensively, little is known of its biologic effects on the lung. To study this problem, the intrapulmonary inactivation of an aerosolized challenge of Staphylococcus aureus was quantified in rats exposed to graded amounts of fresh marijuana smoke. Controls inactivated 85.1 percent +/- 0.3 percent of the bacteria six hours after inoculation. Following an in vivo accumulative exposure to smoke from progressively increasing numbers of marijuana cigarettes for periods of ten minutes each hour for five consecutive hours, intrapulmonary bacterial inactivation was impaired in a dose-dependent manner. Evaluation of the effects of parenterally administered delta-9-tetrahydrocannabinol (THC) or of exposure to...
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Antibacterial activity of Δ9-­tetrahydrocannabinol and cannabidiol

The minimum inhibiting concentrations (MIC) of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for staphylococci and streptococci in broth are in the range of 1–5 μg/ml. In the same range, both compounds are also bactericidal. In media containing 4% serum or 5% blood the antibacterial activity is strongly reduced (MIC 50μg/ml). Gram-negative bacteria are resistant to THC and CBD.
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