Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.
Opioid analgesic overdose mortality continues to rise in the United States, driven by increases in prescribing for chronic pain. Because chronic pain is a major indication for medical cannabis, laws that establish access to medical cannabis may change overdose mortality related to opioid analgesics in states that have enacted them.
- The journal of pain : official journal of the American Pain Society
- Published over 5 years ago
Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic noncancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among subjects with chronic noncancer pain. A standardized herbal cannabis product (12.5% THC) was dispensed to eligible subjects for a one-year period; controls were subjects with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events (SAEs) and non-serious adverse events (AEs). Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and sixteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 215 controls (chronic pain but no current cannabis use) from seven clinics across Canada. The median daily cannabis dose was 2.5g/d. There was no difference in risk of SAEs (adjusted IRR=1.08, 95% CI=0.57-2.04) between groups. Medical cannabis users were at increased risk of non-serious AEs (adjusted IRR=1.73, 95% CI=1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program over one year, appears to have a reasonable safety profile. Longer term monitoring for functional outcomes is needed.
- Philosophical transactions of the Royal Society of London. Series B, Biological sciences
- Published about 8 years ago
The psychoactive component of the cannabis resin and flowers, delta9-tetrahydrocannabinol (THC), was first isolated in 1964, and at least 70 other structurally related ‘phytocannabinoid’ compounds have since been identified. The serendipitous identification of a G-protein-coupled cannabinoid receptor at which THC is active in the brain heralded an explosion in cannabinoid research. Elements of the endocannabinoid system (ECS) comprise the cannabinoid receptors, a family of nascent lipid ligands, the ‘endocannabinoids’ and the machinery for their biosynthesis and metabolism. The function of the ECS is thus defined by modulation of these receptors, in particular, by two of the best-described ligands, 2-arachidonoyl glycerol and anandamide (arachidonylethanolamide). Research on the ECS has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. Many of the former relate to stress-recovery systems and to the maintenance of homeostatic balance. Among other functions, the ECS is involved in neuroprotection, modulation of nociception, regulation of motor activity, neurogenesis, synaptic plasticity and the control of certain phases of memory processing. In addition, the ECS acts to modulate the immune and inflammatory responses and to maintain a positive energy balance. This theme issue aims to provide the reader with an overview of ECS pharmacology, followed by discussions on the pivotal role of this system in the modulation of neurogenesis in the developing and adult organism, memory processes and synaptic plasticity, as well as in pathological pain and brain ageing. The volume will conclude with discussions that address the proposed therapeutic applications of targeting the ECS for the treatment of neurodegeneration, pain and mental illness.
Cannabis has been used to treat pain for thousands of years. However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications. The major psychotropic component of cannabis is Δ9-tetrahydrocannabinol (THC), one of some 120 naturally occurring phytocannabinoids. Cannabidiol (CBD) is another molecule found in herbal cannabis in large amounts. Although CBD does not produce psychotropic effects, it has been shown to produce a variety of pharmacological effects. Hence, the overall effects of herbal cannabis represent the collective activity of THC, CBD and a number of minor components. The action of THC is mediated by two major G-protein coupled receptors, cannabinoid receptor type 1 (CB1) and CB2, and recent work has suggested that other targets may also exist. Arachidonic acid derived endocannabinoids are the normal physiological activators of the two cannabinoid receptors. Natural phytocannabinoids and synthetic derivatives have produced clear activity in a variety of models of joint pain in animals. These effects are the result of both inhibition of pain pathway signalling (mostly CB1) and anti-inflammatory effects (mostly CB2). There are also numerous anecdotal reports of the effectiveness of smoking cannabis for joint pain. Indeed, it is the largest medical request for the use of the drug. However, these reports generally do not extend to regulated clinical trials for rheumatic diseases. Nevertheless, the preclinical and human data that do exist indicate that the use of cannabis should be taken seriously as a potential treatment of joint pain.
The therapeutic application of Cannabis is attracting substantial public and clinical interest. The Cannabis plant has been described as a veritable ‘treasure trove’, producing more than a hundred different cannabinoids, although the focus to date has been on the psychoactive molecule delta-9-tetraydrocannabinol (THC) and cannabidiol (CBD). Other numerous secondary metabolites of Cannabis the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesised to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’. The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardised growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source. Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC:CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of Cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.
Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives.
There has been a significant increase in the prescribing of medication for chronic non-cancer pain. In a UK population sample, we aimed to assess cardio-metabolic (CM) health in those taking these chronic pain medications.
As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes.
Recent analysis of the cannabinoid content of cannabis plants suggests a shift towards use of high potency plant material with high levels of Δ(9)-tetrahydrocannabinol (THC) and low levels of other phytocannabinoids, particularly cannabidiol (CBD). Use of this type of cannabis is thought by some to predispose to greater adverse outcomes on mental health and fewer therapeutic benefits. Australia has one of the highest per capita rates of cannabis use in the world yet there has been no previous systematic analysis of the cannabis being used. In the present study we examined the cannabinoid content of 206 cannabis samples that had been confiscated by police from recreational users holding 15 g of cannabis or less, under the New South Wales “Cannabis Cautioning” scheme. A further 26 “Known Provenance” samples were analysed that had been seized by police from larger indoor or outdoor cultivation sites rather than from street level users. An HPLC method was used to determine the content of 9 cannabinoids: THC, CBD, cannabigerol (CBG), and their plant-based carboxylic acid precursors THC-A, CBD-A and CBG-A, as well as cannabichromene (CBC), cannabinol (CBN) and tetrahydrocannabivarin (THC-V). The “Cannabis Cautioning” samples showed high mean THC content (THC+THC-A = 14.88%) and low mean CBD content (CBD+CBD-A = 0.14%). A modest level of CBG was detected (CBG+CBG-A = 1.18%) and very low levels of CBC, CBN and THC-V (<0.1%). "Known Provenance" samples showed no significant differences in THC content between those seized from indoor versus outdoor cultivation sites. The present analysis echoes trends reported in other countries towards the use of high potency cannabis with very low CBD content. The implications for public health outcomes and harm reduction strategies are discussed.