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Eric Singer

an important might role THC play

manor222
10.10.2018

Content:

  • an important might role THC play
  • Medical cannabis
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  • The importance of heat is often overlooked, particularly since many non-smoked but you can be sure that almost any cannabis medicine you come across will have is widely misunderstood and may, in fact, play a significant role is shaping. The Cannabis plant was grown in ancient times as an important textile crop in they may play an important role in the overall effect of Cannabis strains (). How Sugar Plays A Major Role In Growing Cannabis This might seem like a strange variable, but it's actually one of the biggest factors.

    an important might role THC play

    The main way Canadians will be able to purchase recreational cannabis is through e-commerce, through either provincially or privately-run online stores. While regulations vary between the provinces and territories, some offering brick and mortar stores, some not, on Wednesday each launched an e-commerce site to provide consumers access to marijuana.

    Shopify will be leading the way in Ontario, it was chosen by the provincial government to help run the online sales through the LCBO-owned Ontario Cannabis Store. The Ottawa-based e-commerce giant was also chosen by three other provinces, British Columbia, Newfoundland and Prince Edward Island to build their online retail sites as well run some of the brick and mortar retail sales systems. Shopify Point of Sale https: However, since each province is so different Goble says Shopify has been treating its four contracts as different projects.

    Shopify is helping these four provinces build out their e-commerce operations, but policies and regulations around the sale of cannabis vary between the provinces, some opting for government-run systems, others fully private. In the later cases long-time medical cannabis producers have been able to win the online sales market. This is in line also with the observations of Compton et al. The reasons for the discrepant findings in different strains of CB 1 knockout mice are unknown.

    Clearly, there is as yet only a poor understanding of the actions of cannabinoids in the basal ganglia and cerebellum. Interactions with other chemical signalling systems in the brain are likely to be important.

    Such complexities are likely to prove the norm. There is anecdotal evidence that cannabis can relieve muscle pain and spasticity in patients suffering from multiple sclerosis Consroe et al. Experimental data obtained by Baker et al. Mice immunized with myelin antigens develop spasticity and tremor.

    Both symptoms were ameliorated by administration of cannabinoids, and the symptoms were exacerbated by rimonabant, suggesting the involvement of CB 1 receptors and tonic activity in the endocannabinoid system. The effects of both cannabinoids Lichtman and Martin, and anandamide Mallet and Beninger, were reversed by rimonabant, indicating that they are mediated by the CB 1 receptor. A probable site for these effects is the hippocampus. In each case the animals were unable to segregate information between trials in the task because of disruptions to the processing of sensory information in hippocampal circuits.

    CB 1 receptors are expressed at high densities in the hippocampus. The terminals of these cells surround large pyramidal neuron somata in the CA1—CA4 fields.

    In addition CB 1 receptors are expressed, at a lower level, in the glutamatergic pyramidal cells and their terminals. Cannabinoids can thus inhibit both the release of GABA and glutamate in hippocampal circuits. The mechanisms underlying synaptic plasticity have been studied more intensely in the hippocampus than in any other brain region. The administration of exogenous cannabinoids is, of course, wholly unphysiological and cannot mimic the effects of endocabinnoids that are released in discrete local regions in response to particular patterns of afferent inputs.

    CB 1 receptors are capable of regulating both inhibitory and excitatory neurotransmitter release in the hippocampus and are thus capable of subtle control of synaptic plasticity. One approach to answering the question of what role the tonic release of endocannabinoids may play in hippocampal function has been to examine the effects of CB 1 receptor knockout or of selective CB 1 receptor antagonists.

    Un fortunately, these studies have so far yielded conflicting results. Like other intoxicant drugs cannabis causes profound changes in a variety of higher brain functions. The literature on the acute effects of the drug in human subjects is large, and can only be summarized here for reviews see Jones, ; Solowij, ; Iversen, ; Earleywine, The distribution of CB 1 receptors in the neocortex has been described in detail Herkenham et al.

    As in the hippocampus, the majority of cortical interneurons expressing high levels of CB 1 receptor are GABAergic cells, which also express cholecystokinin Marsicano and Lutz, Despite the obvious importance of the abundant CB 1 receptors in the neocortex there have so far been few electrophysiological studies of their effects on neural activity. The earlier literature, however, contains several reports of the effects of acute and chronic cannabis use on EEG activity, both in man and animals reviewed by Adams and Martin, ; Solowij, In contrast, the CB 1 antagonist rimonabant was shown to induce EEG changes characteristic of arousal in rats, and increased the time spent in wakefulness as opposed to sleep Santucci et al.

    Studies of the effects of cannabis on perceptual abilities have yielded a variety of often conflicting results. While users often report a subjective enhancement of visual and auditory perception, sometimes with synesthesia sounds take on visual colourful qualities , laboratory studies have usually not shown marked changes in visual or auditory perception.

    One subjective effect that has been confirmed is the sensation that cannabis users experience time as passing more quickly relative to real time. In laboratory tests subjects overestimate the amount of elapsed time when asked to estimate, or produce shorter than required intervals when asked to signal a period of elapsed time Hicks et al. This curious effect can also be seen in rats trained to respond for food reward using a fixed interval schedule.

    When treated with THC or WIN55, the animals shortened their response interval, whereas the antagonist rimonabant lengthened this interval Han and Robinson, There have been many studies of the acute and chronic effects of cannabis on human cognitive function Jones, ; Solowij, ; Earleywine, Performance on a variety of tests of cognitive function is impaired by the drug, but by comparison with alcohol the effects of cannabis are subtle.

    Whereas even moderate doses of alcohol, for example, impair reaction time, most studies with cannabis have failed to show consistent effects on measures of simple reaction time. Among the impairments of cognitive function that have been observed in many, but not all, human studies are: On the other hand, intoxicated subjects can perform simple arithmetic, learn simple lists of words and recall memories laid down earlier.

    Other studies have addressed the question of whether more severe deficits in cognitive function might develop in chronic heavy users of cannabis, or in animals treated for prolonged periods with the drug. The human studies are fraught with difficulties, as described in detail by Earleywine Statistical analysis of such data has often been poor, common errors being the use of so many different tests that the likelihood of finding some significant differences is increased, or the use of inadequate sample sizes.

    Other drug use can also confound the data. Results have been very variable. Many studies have suffered from poor design. It is not sufficient to identify a group of cannabis users and simply to test them after stopping cannabis use. At days 0, 1 and 7 the heavy users scored significantly below control subjects on a battery of neuropsychological tests, particularly in recall of word lists.

    However, by day 28 there were virtually no differences between the groups on any of the test results, and no significant association between cumulative lifetime cannabis use and test scores.

    Solowij recruited a group of people who had used cannabis regularly for at least 5 years but who had stopped on average 2 years before the experiment. The subjects were given a very difficult task. They had to listen to a series of tones, some in the right ear some in the left; the tones were long or short but differing by only 51 ms and high or low pitch but differing very little.

    Participants had to press a button as fast as possible in response to longer tones of a specified pitch in the correct ear. Previous research using this paradigm showed that current regular cannabis users had difficulty in discriminating between the tones. Many subjective reports suggest that cannabis intoxication is associated with an increased appetite, particularly for sweet foods, even in subjects who were previously satiated.

    This effect can be confirmed under laboratory conditions Hollister, ; Mattes et al. The endocannabinoid anandamide also stimulates food intake in rats, and the effect is blocked by rimonabant Williams and Kirkham, These results suggest that cannabinoids may play a role in the regulation of food intake and body weight Mechoulam and Fride, At some stages during development these effects of endocannabinoids may be of critical importance.

    The ability of THC and the synthetic cannabinoid nabilone to control the nausea and vomiting associated with cancer chemotherapy is one of the few well documented medical applications for these drugs for reviews of the controlled clinical trials see Vincent et al. THC dronabinol and nabilone were approved for medical use in the USA, although neither drug has found much utility.

    Endogenous cannabinoids and cannabinoid receptors exist at various levels in the pain pathways, from peripheral sensory nerve endings to spinal cord and supraspinal centres, in a system that is parallel to but distinct from that involving endorphins and opiate receptors.

    Behavioural studies have shown that cannabinoids reduce thermal and mechanical allodynia in rat models of neuropathic pain Herzberg et al. Furthermore, noxious stimulation evoked an increased release of anandamide in the periaqueductal grey region of brainstem, a key site for modulating nociceptive information Walker et al.

    Thus, although Di Marzo et al. Alternatively, it has been proposed that the effects of anandamide might be mediated through its ability to bind to the vanilloid VR1 receptor, which is present in primary afferent neurons and known to play an important role in nociceptive responses Di Marzo et al. To complicate matters further, Zimmer et al. The reasons for the discrepant results obtained with different strains of CB 1 receptor knockout mice are unknown.

    There is evidence for an interaction between cannabinoid and opioid mechanisms. In tests of acute pain Fuentes et al. This potentiation could be blocked by either rimonabant or by naloxone, indicating that both CB 1 and opiate receptors were involved Fuentes et al. An electrophysiological analysis of the effects of cannabinoids on single cell firing patterns in RVM revealed that the effects of cannabinoids were similar to those elicited by morphine. The authors concluded that cannabinoids may produce analgesia through activation of a brainstem circuit that is also required for opiate analgesia, although the two mechanisms are pharmacologically distinct.

    Basic research into the role of cannabinoids and endocannabinoids in pain mechanisms is progressing rapidly. Clinical progress, however, has been slow. The experience is highly variable, depending on the dose of drug, the environment and the experience and expectations of the drug user.

    The user feels relaxed and calm, in a dreamlike state disconnected from real world. The intoxicated subject often has difficulty in carrying on a coherent conversation, and may drift into daydreams and fantasies.

    Drowsiness and sleep may eventually ensue. The feelings of heightened perception, increased appetite and distortion of the sense of time have already been referred to. A survey of young British cannabis users Atha and Blanchard, reported that the most common positive benefits reported were relaxation and relief from stress The intoxicant effects are clearly mediated via CB 1 receptors.

    The CB 1 antagonist blocked the acute psychological effects of the active cigarettes. Interestingly rimonabant itself when given alone with placebo cigarette produced no significant psychological effects. Self ratings of cannabis intoxication correlated most markedly with increased blood flow in the right frontal region. Endocannabinoids and CB 1 receptors are present in many regions of the limbic forebrain.

    For example, Katona et al. Electrophysiological experiments showed that cannabinoids modulated GABAergic synaptic transmission. The authors suggested that such effects might underlie some of the actions of cannabinoids on emotional behaviour.

    Other experiments have revealed that, in common with other euphoriant drugs, THC selectively activates dopaminergic neurons in the ventral tegmental area. In an electrophysiological study French et al. Many animal studies have shown that tolerance develops to most of the behavioural and physiological effects of THC for review see Pertwee, The earlier clinical literature suggested that tolerance also occurs after repeated administration of THC in man, although many of these studies were poorly controlled for reviews see Jones, , ; Hollister, But for many years cannabis was not considered to be a drug of addiction.

    Attitudes have changed markedly in recent years. In the USA, Anthony et al. More carefully controlled studies have also shown that a reliable and clinically significant withdrawal syndrome does occur in human cannabis users when the drug is withdrawn. The symptoms include craving for cannabis, decreased appetite, sleep difficulty and weight loss, and may sometimes be accompanied by anger, aggression, increased irritability, restlessness and strange dreams Budney et al.

    The existence of dependence on cannabinoids in animals is also much more clearly observable because of the availability of CB 1 receptor antagonist drugs that can be used to precipitate withdrawal. Thus, Aceto et al. The syndrome included scratching, face rubbing, licking, wet dog shakes, arched back and ptosis—many of the same signs are seen in rats undergoing opiate withdrawal.

    An electrophysiological study showed that precipitated withdrawal was also associated with reduced firing of dopamine neurons in the ventral tegmental area of rat brain Diana et al.

    These data indicate clearly that chronic administration of cannabinoids leads to adaptive changes in the brain, some of which are similar to those seen with other drugs of dependence. The ability of THC to cause a selective release of dopamine from the nucleus accumbens Tanda et al. THC is difficult to administer intravenously and these authors succeeded perhaps in part because they succeeded in delivering the drug intravenously in doses comparable to those to which human cannabis users are exposed.

    The potent synthetic cannabinoids are far more water soluble than THC, which makes intravenous administration easier. Another way of demonstrating the rewarding effects of drugs in animals is the conditioned place preference paradigm, in which an animal learns to approach an environment in which it had previously received a rewarding stimulus. A number of studies have suggested that there may be links between the development of dependence to cannabinoids and to opiates Manzanares et al.

    Rats treated chronically with the cannabinoid WIN55, became sensitized to the behavioural effects of heroin Pontieri et al. Such interactions can also be demonstrated acutely. A synergy between cannabinoids and opiate analgesics has already been described above.

    The availability of receptor knockout animals has also helped to illustrate cannabinoid—opioid interactions. These findings point clearly to interactions between the endogenous cannabinoid and opioid systems in CNS, although the neural circuitry involved remains unknown. Although there have been claims that chronic cannabis use may permanently damage the brain, there is little scientific evidence to support these claims for reviews see Dornbush et al.

    The earlier studies have been complemented by the application of powerful modern neuroimaging methods. Animal studies have yielded conflicting results. Treatment of rats with high doses of THC given orally for 3 months Scallet et al.

    Although claims were made that exposure of a small number of rhesus monkeys to cannabis smoke led to ultrastructural changes in septum and hippocampus Harper et al. Studies of the effects of cannabinoids on neurons in vitro have also yielded inconsistent results. Concentrations of THC as low as 0. The antagonist rimonabant blocked these effects, but not pertussis toxin.

    The authors proposed a toxic mechanism involving arachidonic acid release and formation of free radicals. Some studies have reported neuroprotective actions of cannabinoids.

    Administration of WIN55, was found to reduce cerebral damage in rat hippocampus or cerebral cortex after global ischaemia or focal ischaemia models in vivo Nagayama et al. THC had a similar effect in vivo in protecting against damage elicited by ouabain Van der Stelt et al. But not all of these effects seem to require mediation via cannabinoid receptors.

    Both THC and cannabidiol, which is not active on cannabinoid receptors, protected rat cortical neurons against glutamate toxicity Hampson et al. The authors suggested that the protective effects of THC in their studies might be due to the antioxidant properties of these polyphenolic molecules, which have redox potentials higher than those of known antioxidants e.

    The mixed reports of neurotoxic and neuroprotective effects of cannabinoids are confusing. While it may be possible to demonstrate neurotoxic actions after exposure of neurons to high concentrations of cannabinoids in vitro , there is little evidence for any significant neural damage in vivo after the administration of pharmacologically relevant doses of these drugs.

    Research psychiatrists, particularly in Britain Thomas, ; Hall and Degenhardt, ; Johns, , have studied this condition carefully. It nearly always results from taking large doses of the drug, often in food or drink, and the condition may persist for some time, perhaps as the accumulated body load of THC is washed out. The low bioavailability is largely attributed to significant first-pass metabolism in the liver and erratic absorption from the gastrointestinal tract.

    Due to the poor bioavailability of oral preparations, alternative routes of administration have been studied, including sublingual and rectal.

    These alternative formulations maximize bioavailability and reduce first-pass metabolism. Like cannabinoid absorption, distribution is also dependent on route of administration. Smoking and inhalation of vaporized cannabis have better absorption than do other routes of administration, and therefore also have more predictable distribution. It distributes rapidly to highly vascularized organs such as the heart, lungs, liver, spleen, and kidneys, as well as to various glands.

    Low levels can be detected in the brain, testes, and unborn fetuses, all of which are protected from systemic circulation via barriers. DeltaTHC is the primary molecule responsible for the effects of cannabis. Ingestion of edible cannabis products lead to a slower onset of effect than the inhalation of it because the THC travels to the liver first through the blood before it travels to the rest of the body.

    Inhaled cannabis can result in THC going directly to the brain, where it then travels from the brain back to the liver in recirculation for metabolism.

    Smoking has been the means of administration of cannabis for many users, but it is not suitable for the use of cannabis as a medicine. The US Food and Drug Administration FDA has not approved smoked cannabis for any condition or disease, as it deems that evidence is lacking concerning safety and efficacy.

    Since ancient humans used hemp seed as food, it was quite natural for them to also discover the medicinal properties of the plant.

    He recommended the substance for many ailments, including constipation, gout, rheumatism, and absent-mindedness. The Ebers Papyrus c. Surviving texts from ancient India confirm that cannabis' psychoactive properties were recognized, and doctors used it for treating a variety of illnesses and ailments, including insomnia, headaches, gastrointestinal disorders, and pain, including during childbirth. The Ancient Greeks used cannabis to dress wounds and sores on their horses, [93] and in humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis seeds were used to expel tapeworms.

    In the medieval Islamic world , Arabic physicians made use of the diuretic , antiemetic , antiepileptic , anti-inflammatory , analgesic and antipyretic properties of Cannabis sativa , and used it extensively as medication from the 8th to 18th centuries.

    Cannabis seeds may have been used for food, rituals or religious practices in ancient Europe and China. Widely cultivated strains of cannabis, such as "Afghani" or "Hindu Kush", are indigenous to the Pakistan and Afghanistan regions, while "Durban Poison" is native to Africa. The use of cannabis in medicine began to decline by the end of the 19th century, due to difficulty in controlling dosages and the rise in popularity of synthetic and opium -derived drugs. In the United States, the medical use of cannabis further declined with the passage of the Marihuana Tax Act of , which imposed new regulations and fees on physicians prescribing cannabis.

    Pharmacopeia in , and officially banned for any use with the passage of the Controlled Substances Act of Cannabis began to attract renewed interest as medicine in the s and s, in particular due to its use by cancer and AIDS patients who reported relief from the effects of chemotherapy and wasting syndrome. The use of cannabis, at least as fiber, has been shown to go back at least 10, years in Taiwan. In Mexico , THC content of medical cannabis is limited to one percent. Article 2 provides for the following, in reference to Schedule IV drugs:.

    A Party shall, if in its opinion the prevailing conditions in its country render it the most appropriate means of protecting the public health and welfare, prohibit the production, manufacture, export and import of, trade in, possession or use of any such drug except for amounts which may be necessary for medical and scientific research only, including clinical trials therewith to be conducted under or subject to the direct supervision and control of the Party.

    The convention thus allows countries to outlaw cannabis for all non-research purposes but lets nations choose to allow use for medical and scientific purposes if they believe total prohibition is not the most appropriate means of protecting health and welfare. The convention requires that states that permit the production or use of medical cannabis must operate a licensing system for all cultivators, manufacturers, and distributors and ensure that the total cannabis market of the state shall not exceed that required "for medical and scientific purposes".

    In the United States, the use of cannabis for medical purposes is legal in 33 states, four out of five permanently inhabited U. In December , however, the Rohrabacher—Farr amendment was signed into law, prohibiting the Justice Department from prosecuting individuals acting in accordance with state medical cannabis laws.

    The method of obtaining medical cannabis varies by region and by legislation. In the US, most consumers grow their own or buy it from cannabis dispensaries in states where it is legal. In the United States, health insurance companies may not pay for a medical marijuana prescription as the Food and Drug Administration must approve any substance for medicinal purposes.

    Before this can happen, the FDA must first permit the study of the medical benefits and drawbacks of the substance, which it has not done since it was placed on Schedule I of the Controlled Substances Act in Therefore, all expenses incurred fulfilling a medical marijuana prescription will possibly be incurred as out-of-pocket.

    Organizations that have issued statements in opposition to the legalization of medical cannabis include the American Academy of Pediatrics , [10] American Psychiatric Association , [] and American Society of Addiction Medicine. The American Medical Association [] and American College of Physicians [] do not take a position on the legalization of medical cannabis, but have called for the Schedule I classification of cannabis to be reviewed.

    The American Academy of Family Physicians similarly does not take a position, but does support rescheduling in order to facilitate research. As an antiemetic , these medications are usually used when conventional treatment for nausea and vomiting associated with cancer chemotherapy fail to work. Nabiximols is used for treatment of spasticity associated with MS when other therapies have not worked, and when an initial trial demonstrates "meaningful improvement".

    Relative to inhaled consumption, peak concentration of oral THC is delayed, and it may be difficult to determine optimal dosage because of variability in patient absorption. In , Albert Lockhart and Manley West began studying the health effects of traditional cannabis use in Jamaican communities. They developed, and in gained permission to market, the pharmaceutical "Canasol", one of the first cannabis extracts.

    Medical cannabis research includes any medical research on using cannabis as a treatment for any medical condition. For reasons including increased popular support of cannabis use, a trend of cannabis legalization , and the perception of medical usefulness, more scientists are doing medical cannabis research.

    Medical cannabis is unusually broad as a treatment for many conditions, each of which has its own state of research. Similarly, various countries conduct and respond to medical cannabis research in different ways. From Wikipedia, the free encyclopedia. Part of a series on Cannabis Arts Culture. Drug culture Illegal drug trade Psychedelia.

    Long-term effects of cannabis. History of medical cannabis. Cannabis indica fluid extract, American Druggists Syndicate, pre An advertisement for cannabis americana distributed by a pharmacist in New York in Legality of cannabis by country.

    Legal as authorized by a physician. Legal for any use no prescription required. Medical cannabis in the United States. Cannabis portal Medicine portal. National Institute of Drug Abuse. Retrieved 19 April The term medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat a disease or symptom.

    Retrieved 8 September A Systematic Review and Meta-analysis". Current Pain and Headache Reports. A review of their therapeutic potential". Journal of Ethnopharmacology Review. Retrieved 30 July National Conference of State Legislatures. Retrieved 3 July Does Medical Marijuana Work?

    Retrieved 24 May Marijuana Use During Pregnancy and Lactation". Psychosomatics Review, case series. The Cochrane Database of Systematic Reviews. Annals of Internal Medicine. A Meta-analysis of Individual Patient Data". The Journal of Pain. Systematic review of randomized controlled trials". British Journal of Clinical Pharmacology Review. Medical Science Monitor Review. Revista De Neurologia Review in Spanish.

    Marijuana Cannabis sativa L. Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Retrieved 7 May There is clear evidence that recreational cannabis can produce a transient toxic psychosis in larger doses or in susceptible individuals, which is said to characteristically resolve within a week or so of absence Johns

    Medical cannabis

    The marijuana plant features broad leaves, dense buds, and has a bushy appearance. Over the years, hemp has played an important role in the We can see how important hemp has been in the history of the human race. Limited data suggest that health care providers also may consider this . 2C9 and 3A4 play a significant role in the primary metabolism of THC and CBN. Keywords: cannabinoids, terpenoids, essential oils, THC, CBD, limonene, pinene , ): 'This type of synergism may play a role in the widely held (but not.

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    Comments

    kostak

    The marijuana plant features broad leaves, dense buds, and has a bushy appearance. Over the years, hemp has played an important role in the We can see how important hemp has been in the history of the human race.

    serega270978

    Limited data suggest that health care providers also may consider this . 2C9 and 3A4 play a significant role in the primary metabolism of THC and CBN.

    junior6111

    Keywords: cannabinoids, terpenoids, essential oils, THC, CBD, limonene, pinene , ): 'This type of synergism may play a role in the widely held (but not.

    xlopka

    These compounds, he explains, apparently play an important role in such basic . By now nearly everyone has heard that cannabis can play a palliative role for .

    OdIgI

    I would like to discuss two aspects of the work FDA does related to the regulation of marijuana. First, FDA plays a critical role in regulating the development and.

    marfol1

    This may play an important role in the control of neural circuits, particularly in cerebellum and hippocampus (see below). Exogenously administered THC or.

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