the medical literature about marijuana was issued by a White House- commissioned committee of ii . These are critical components of the immune system and could seri- gram was terminated, in the government's opinion, because too many people . tions with the DEA and with exclusion from participation in. Medicare. current thoughts on medical marijuana. Think about the . Synthetic cannabinoids - are those which have been man-made (Rx or chemical) . However, as a component of the cannabis/marijuana plant it is a Schedule I Sometimes referred to as “Realm Oil”. A therefore excluded from DEA rule. CBD's other medicinal effects stem from completely separate pathways, such as the cannabinoid receptor 2 (CB2), Thoughts on those who exclude THC or other cannabis components from the realm of medicinal cannabis?.
realm who Thoughts exclude from or components on cannabis? of THC cannabis medicinal the other those
Cannabis in this context is self-prescribed. Ideally, everyone would go to the doctor to get the best medication for their condition. But out there in the scary real world, people self-medicate. So even if the Department of Health believes there is not enough evidence into the efficacy of medicinal cannabis, if they were being consistent!!! There never was and never has been any justification for prohibition for medicinal or recreational use. If a standardised product was available for non medical use presumably the medical issue would be largely academic — as I assume it is in the Netherlands.
I cannot thank you enough for addressing this issue. I have contacted you privately a few times this last year and your representation and yourself have always treated me with great respect and courtesy. In this particular subject matter and battle, the UK is one of the last to — not only maintain these unethical methods — but we have actually increased the intensity of the disregard for the ill and infirm.
As a lawful and moral citizen, you can imagine the feelings I have towards my own country. I look to the rest of the world with furious envy in so many differing ways. For me, being on the front line of this subject matter, it is hard not to address this through an emotionally invested stance.
Through my own means and the help of others, I now have an outlet for my frustrations through my blog:. The fact we have to pour our lives over the net and beg the press who invariably turn a blind eye just to make a difference and a point.
The ravaged dignity for those of us who are extremely private is a part of this battle which will never heal; these scars are terminal for pride. Our families need due recognition too as they are the forgotten braves of this war.
I am privileged to now have a network of colleagues and friends who have saved sanity when breaking point reaches ever nearer. Its a disgrace that people with genuine health needs are being punished for seeking relief from cannabis, more so when fellow European citizens can access it and transport it freely across Europe even the UK!.
Cannabis which is pretty much non toxic, therefore surely it cannot be measured in the same way as drugs of addiction, to criminalise people for using it recreationally when a far more dangerous substance is legally available in supermarkets across the land is plain wrong, to persecute people deriving medicinal benefit is scandalous and the home office should be ashamed of themselves. The major supermarkets feed the addictions of s of alcoholics without remorse daily because of the caveat that people should drink responsibility a contradiction in terms.
The figures also come from a report that excluded people in treatment services, the homeless and those in supported housing, this would add ,s to the dependency list, cleverly the home office decided to use the figures away, its deceptive in my opinion.
The link is for the report, the home office used for some of the figures for alcohol. The home office of course, because of the massive revenues generated by alcohol cannot upset the alcohol industry too much or indeed deter drinkers too much, because the UK would be bankrupt without alcohol!
Millions of jobs would be lost. Can you imagine the same for cannabis? Most people accept if alcohol was discovered today it would be an A class drug! Addiction of any kind should be a health issue not a criminal justice issue! Double punishment for heroin addicts, the pain of addiction and of course a criminal record!
Surely much of the debate would be solved if we required those doing the prohibiting to provide the evidence supporting their policy. Another thing to remember is that, over the years, many parties? How to get around this? And how do we do it within the Home Office guidelines of today?
Also, just as a thought, how do Homeopathic remedies get a thumbs up and how would the burden of proof be applied to them? In a ruling that took aim at those advocating an end to the current criminal prohibition on marijuana the court said disagreeing with the law does not permit you to break it.
Court of Appeal judgment Wednesday that said such behaviour undermines the rule of law. What I would argue from the Drug Equality Alliance perspective is that it is the govt who are not obeying the rule of law. Totally behind you with this professor. I for one am fed up of this Orwellian system that we live in. As you rightly advocate, we need to be a lot more grown up about the whole drug issue.
We are big boys and girls, and dont need dictators teling us what we can or cannot use in the privacy of our own homes, if it inflicts no harm on others. We need education about drugs, research and an open culture. We must exercise our right to freedom. Some were clearly stupid; thinking that drinkers would be deterred from behaving badly when drunk for fear of legal sanctions misses the point that many people get drunk deliberately to lose the inhibitions that such sanctions … Read More […].
We really have to get our act together and fight cannabis prohibition. Those ministers who refuse even to consider medicinal use can only be described as evil. At best they are cowardly, indolent and cruel. At worst they are corrupt, oppressive and sadistic. Medical use of cannabis is a great idea for sure, but not what we should be arguing for, we want equality of treatment for all.
I am more concerned with pragmatism, even, dare I say it, expediency. Anything, short of violence, that will break through the inertia that maintains this prohibition is justifiable. The medicinal cannabis argument is irrefutable. It is an unlocked door waiting to be pushed open. We should be able to shame and embarrass ministers into change. It is a scandal that they deny relief to those in suffering. Well just the persons locked up behind your political open door.
Amnesty now for all prisoners of the war. I want consensus too, but not on these terms. Having tried repeatedly to be inclusive and supportive with you, you just convinced me that your whole approach is just a semantic game and, therefore, meaningless. Only because my last post coincided in time with yours do I say you take it in the wrong way. What you just posted makes no sense at all, you must be upset about it. What is it you truly want me to believe?
This is jour job? A bandleader we should all sign up to? Just what eactly for Peter? So we can lobby for what exactly Peter? Where is the political door open Peter?
Which prisoner can walk free tonight for all your talk you have promised little to offer for the desperate plight people experience thanks to a lot more than you or anyone else not getting cannabis legally.
Open up the eyes to see what you are asking for? Ask yourself what level this claim inspires, empathy for the sick? It is a freeeom of thought we must see it in terms of liberty, relatively proportionate tests of incursions into liberty. We want our freedom. Yes, Darryl, we all want our freedom. To unlock the prison we are in we need a key that fits the lock. That might have been relevant back when the prison was built.
That means we have to work within the existing political system, by its rules. Denying people in pain and suffering the relief they need is evil.
I shall try to fight the evil first and worry about the immorality later. You bring nothing to this again. I can tell you enjoy it but it has no point. If you like, I can put some medicinal users in touch with you and maybe you could do some of the letter writing and lobbying?
It would be a great help. There is no point in meeting with or writing to ministers about medical cannabis from my view as I find the whole idea abhorrent — being sick to claim freedom when the only valid approach would be a libertarian one. They used to think gays were sick and some argued they were not bad, as in not needing punishment but suffering from illness needing treatment. In your mind we are so weak that we could only expect cannabis to be available for the few who obviously would benefit, and then that would open the door you think to liberty.
Wrong, there is no conection between freedom of thought for ordinary people as a right and special entitlements for the sick. One does not lead at all from the other. Take it head on, but get out of your prescription comfort zone or going on about importing some cannabis from Holland for someone. I think we shall have to agree to differ Darryl because in my view, most of what you say is meaningless waffle.
I think your stance is pretentious, unrealistic and incredibly naive. Is this comment by necessity or just nastiness? Darryl, why are you behaving like a particularly unpleasant and aggressive troll? Your esoteric and bizarre approach to the subject is different from mine but please run your arguments if you wish.
You have my support. I can see the tortuous logic in your approach but I doubt that it will be effective. What will not work is your intemperate language, impugning of my motives or wholly inaccurate description of my campaigning. If you want to continue trying to persuade me towards your approach I suggest you email me: David, I truly admire your rational and courageous arguments on this subject.
Long may that continue! In other words, watch your back. Perhaps we must first think what do we mean by medical user and what role a doctor need play. After reading, or attempting to read, the last posts all I can say is this.
My next step is sending a picture of myself along with my name and address to the home office. Police station everyday, pics of me consuming on the net. But have we no other forms of attacking these unjust laws?
Even a full expose of the comments pages of the mail could get us further than we are at the moment. So please, have a go at finding some common ground and carry on in your own inimitable ways or kiss and make up. Find some common ground!!! Arguing from the get go is just sad. I like you both. I read what you publish and follow your blogs and sites with interest. Bet you hate me to now…but I had to have a rant. Thing is, one group says head due East and other says due West, they compromise and go nowhere.
My input is about seeking a focused direction based upon an analysis that is in broad terms, irrefutable. This is based upon our linguistic exactitude re the law and the controls we are all complaining about and our legal analysis. The problem we have identified has a solution that is intollerant of discussing he issue in old terms, ie using prohibitionist speak. Those who refuse to use what they know to be correct are simply not a friend to the cause I am fighting for,even though they insist tehy are doing great work, sadly they are not in my view, they just compound the problem by muscling for media attention and then blowing it by using ineffectual terms and making weak demands.
Yes Nik, at this point it would be wiser to amalgamate than fragment. In order to present a united front it would be better to resolve differences of opinion through private communication between the parties involved. I believe Professor Nutt is probably the most respectable spokesman we have had yet. He is not a crank or obvious user himself. He does not condemn recreational or spiritual users and he sends out a message more likely to be accepted by the youth than the see-through bullshit from one government after another since I was a kid.
This means doctors are being forced to violate their Hippocratic oath. I admire your own courage but please be careful about your stated intention of tackling the Home Office head-on as an individual. You remind me of myself. Since I made a public stance of refusing to comply with a law that is so obviously corrupt. I carried on with the idea it was better to demonstrate defiance by publicly sharing the benefits I got from cannabis than to keep on hammering away with rational arguments that are continually ignored.
Instead, all my pro-cannabis videos on the newly-started YouTube were just quietly pulled down and I was successfully framed as a Sex Offender supposed to have groped a nurse while unconscious in hospital.
Certainly no reason for me to stay in Scotland now. As you say, we all need to push together now and not against each other. I think David Nutt is a good figurehead for sanity on all drugs. Thanks for the support. Letter after letter after letter. By using the web site http: Many thanks for both your replies. I was expecting to get lambasted. The decrease in middle cerebral blood velocity is seen with mild and major instances of orthostatic hypotension associated with marijuana after 10 minutes   and not related to plasma THC content.
When looking at the hemispheres of the brain there appears to be an increase in cerebral blood flow relative to placebo inhalation between minutes no longer present at the two hour mark in both hemispheres and globally, which is dose-dependent. Preclinical studies have noted that the CB1 receptor is expressed in brain regions important for sensing and responding to pain nociception ,    suggesting that the cannabinoids may play an important role in nociceptive transmission.
The effect of CB1 activation on pain dissociation can occur in those who have never used marijuana before  and has a rapid onset, occurring within 45 minutes of inhalation. Marijuana is well known to increase hunger, a major cause of the 'munchies' in recreational users.
The appetite-increasing effects of marijuana have also found medicinal use however, to bolster appetite in patients with HIV, cancer, or other diseases associated with muscle-wasting cachexia. Ghrelin ultimately increases food intake via signaling in the hypothalamus, in part via increased hypothalamic AMPK activity, a central control point for nutrient sensing. Interestingly, the requirement of CB1 activation for ghrelin appetite-inducing effects may occur in the periphery rather than the central nervous system, as CB1 receptor antagonists that cannot reach the brain are still highly effective in blocking the appetite-increasing effects of centrally administered ghrelin.
In addition to increasing ghrelin levels,  inhalation of cannabis in HIV patients blinded has been noted to reduce levels of the appetite suppressing peptide PYY.
In heavy marijuana users average six sessions weekly with 5. Chronic marijuana usage has been associated with a reduction in motivation ie. A randomized trial in heavy marijuana users consumption of at least 4 times per week for at least 2 years found that acute marijuana use with medium-dose THC 5.
A systematic review of the effects of cannabinoids including marijuana use was recently completed, and overall found mixed results and general study quality to be poor, with most studies done in the short-term, with a high risk of bias, and done mainly on small and limited populations in North America only.
Endocannabinoids are thought to have a protective effect in epilepsy, since they are released from neurons when a seizure occurs  and control seizure frequency and duration via activating CB1 receptors. The anti-epileptic activity of CB1 receptor activation  is thought to occur via formation of a heterodimer between CB1 and the NMDA receptor, which functions to suppress glutamate signaling.
Excessive glutamate signaling promotes seizures by activating NMDA, which then increases calcium influx and the production of intracellular Nitric Oxide via increased nNOS activity which becomes oxidized to form peroxynitrate. Subsequent peroxynitrate-induced Zinc release in neurons then increases excitatory signaling from glutamate leading to dysregulated neuronal firing. Cannabidiol CBD is a nonpsychoactive bioactive in marijuana which is primarily looked into for epilepsy.
Rather than acting upon the CB1 receptor it is thought to act on the TRPV1 calcium channel, seen in vitro to activate and rapidly desensitize this channel  ultimately resulting in less potential for hyperexcitation.
While only five studies were available for establishing a temporal relationship between marijuana use and anxiety by measuring the same individuals at two time points it does seem that people who used marijuana early on had an increased risk of developing anxiety later in life compared to users who did not use marijuana OR of 1.
In heavy adolescent and adult marijuana users approximately daily usage there does not appear to be any increased risk for depression in later in life when compared to non-smokers. A mildly increased risk for diagnosis of combined depression and anxiety in subjects who chronically use marijuana was noted in another meta-analysis OR of 1. The effects of marijuana memory and learning can be divided up into short, medium, and long-term effects.
In the short term within hours of smoking , marijuana has consistently been shown to impact working and short-term memory. Another meta-analytic study of the non-acute effects of marijuana found small but significant effects on learning and forgretting, but noted a few caveats: CB1 receptor agonists have been shown to suppress NMDA glutamate receptor-mediated calcium influx,  resulting in less CREB phosphorylation and decreased synaptic plasticity that may ultimately impair memory formation.
Inhalation of marijuana smoke is known to increase heart rate at rest. Increases in heart rate upon smoking marijuana can occur even in heavy users  and have been suggested to correlate with the percieved high.
Marijuana-induced increases in heart rate can be attenuated with beta-blockers   or atropine  , the combination of which nearly abolish any changes in heart rate  or other cardiac measures.
The cannabinoid receptor CB1 has been detected in endothelial cells from the human aorta  where its activation leads to increased free radical production and Mitogen-Activated Protein Kinase MAPK activation which leads to cell death. Atherosclerosis is a disease that is driven by chronic inflammation, where fatty deposits and immune cells enter the walls of blood vessels causing progressive narrowing and restriction of blood flow.
It has been noted that cannabinoids have both immunosuppressive and anti-inflammatory properties,    suggesting they may have potential as therapeutics for atherosclerosis. Consistent with this idea, human foam cells, which are damaged macrophages that develop after engulfing oxidized lipids,  have been found to have greater amounts of CB2 than the macrophages from which they are derived.
Activation of the CB2 receptor appears to work via reducing the amount of oxidized LDL cholesterol oLDL that is accumulated by macrophages, secondary to downregulating the binding protein CD36 aka. There may be an efflux of cholesterol out of already-formed foam cells secondary to CB2 activation, since it has been noted that CB2 activation has caused an increase in ATP-Binding Cassette sub-family G member 1 ABCG1 protein levels,  which is responsible for transporting excess cholesterol out of cells.
In contrast to CB2, activation of the cannabinoid signaling system through the CB1 receptor is proatherogenic   although some compounds that inhibit CB1 also have confounding actions which may also be beneficial direct acyl CoA: CB1 receptor activation has been shown to promote cholesterol accumulation in macrophages, leading to foam cell formation. Although macrophages are traditionally considered as the source of foam cell formation, resident vascular smooth muscle cells are also capable of developing into foam cells.
Increased blood pressure may be partly driven by the action of THC on CB1 receptors in the brain, which is known to increase heart rate and produce acute increases in blood pressure. Abrupt cessation of marijuauna usage usage at least 25 times monthly for minimum of one year was associated with an increase in systolic 7. In vitro evidence suggests that some components of marijuana may inhibit platelet aggregation by blocking ADP-induced platelet aggregation.
Serotonin is taken up and stored by platelets; when these platelets are activated, serotonin is released, which functions both as a vasoconstrictor as well as an activator of additional platelets. An in vitro study found that the inhibition of serotonin release by cannabinoids was not correlated to their ability to inhibit platelet aggregation. Although present in rats, the effects of marijuana on triglycerides do not appear to occur in humans.
A large longitudinal study examining marijuana usage found a correlation between marijuana use and elevated triglyceride levels in young users, although this correlation disappeared when concurrent alcohol use was taken into account. Observational studies have failed to note changes in total cholesterol levels among marijuana users,  and either a decrease,  increase,  or no change   in HDL-C. No interventional research concerning the effects of active components of marijuana on cholesterol has been performed to date.
When total cholesterol and LDL-C are investigated, similar mixed results are noted, with one study reporting a possible decrease  and another reporting no significant changes. Although not currently well understood, the mechanisms responsible for marijuana-induced reduction in fasting insulin may occur via attenuation CB1 receptor signaling that could increase adiponectin levels,  resulting in increased insulin sensitivity  and therefore reduced production of insulin.
Moreover, in addition to containing the cannabinoid receptor agonist THC, marijuana also contains cannabidiol, which is a cannabinoid receptor antagonist. Thus, it is plausible that known or yet-to be identified components of marijuana may reduce fasting insulin concentrations via an adiponectin-mediated mechanism that is driven by decreased signaling through the CB1 receptor. Insulin sensitivity as calculated by the Homeostasis Model Assessment of Insulin Resistance HOMA-IR was observed to be higher in current users of marijuana used at least once in the past 30 days when compared to controls who never used marijuana.
No dose-dependency between marijuana use and insulin sensitivity was noted, however. However, the study of chronic users did reveal an increase in adipocyte insulin resistance despite no change in the other measures of insulin sensitivity. There are no clinical studies on the effects of marijuana on glycogen. However, some data from animal models and in vitro experiments do exist.
In animal models, acute administration of cannabis extract to rats decreases glycogen stores in the liver,  while repeated exposure to cannabis extract decreases uterine glycogen stores in rats. Indirect in vitro evidence using human tissue suggests that the cannabinoid system may affect glycogen levels. AMP-activated protein kinase AMPK functions as a cellular energy sensor, inhibits glycogen synthesis in muscle cells, and is involved in a number among other metabolic processes associated with energy homeostasis.
However cellular and molecular control of energy homeostasis is quite complex, requiring a number of other receptors and signaling pathways that also play a role and complicate the picture. A collection of case studies has suggested that marijuana usage may 'mask' ketoacidosis, with less than expected increases in blood acidity relative to ketone concentration and symptoms.
This ketonuria was remedied with intravenous insulin. In a cross-sectional analysis of NHANES data, it appears that current or past marijuana users were at a lower risk of having type II diabetes when compared to those who never used marijuana overall OR 0.
In this study past users, OR 0. Both marijuana  and the endogenous cannabinoid anandamide   have orexigenic appetite increasing effects. It was noted in one study that the appetite-increasing effects of ghrelin, an orexigenic peptide, were blocked by the cannabinoid receptor antagonist rimonabant,  suggesting the some of the appetite increasing effects of marijuana occur via increased ghrelin levels.
Moreover, rimonabant also reduced ghrelin secretion, leading to reduced food intake in food deprived rats. The hypothalamus is highly enriched in CB1 receptors,   and it has been demonstrated in rodents that rimonabant blocks the appetite-stimulating effects of ghrelin when infused directly into this region of the brain.
Marijuana also has been shown to directly increase ghrelin levels in humans. In a prospective subgroup analysis of a trial investigating the effect of smoked cannabis on neuropathic pain in HIV-positive men,  inhalation of marijuana was noted to increase circulating ghrelin by Inhalation of marijuana over a week has also been noted to increase circulating levels of leptin to a large degree in one preliminary trial in an HIV-infected population It is not clear whether the counterintuitive marijuana-induced increase in leptin levels may be population-specific, or even of functional significance.
Given the effects of marijuana on ghrelin, it is possible that leptin levels may increase as part of a negative feedback mechanism. Because calorie intake was not monitored in the HIV study,  it also cannot be ruled out that the increase in leptin levels may have occurred via increased food intake, a known stimulus for leptin production. It has been noted that cannabinoids, similar to the peptide ghrelin,   can directly suppress lipolysis in adipocytes via CB1 activation resulting in an increase in lipid accumulation.
This causes a shift in energy utilization away from fatty acids and towards glucose. Glucose uptake into adipocytes also appears to be enhanced subsequent to CB1 activation,  despite decreased AMPK activity. Other studies assessing the anti-lipolytic effects of cannabinoids have found a suppression of peripheral AMPK mostly in visceral fat tissue  as well as carnitine palmitoyltransferase 1 CPT1   in adipose and hepatic tissue despite both being elevated in neuronal tissues.
The endocannabinoid system appears to have a location-specific influence, and during the state of obesity subcutaneous body fat exhibits a relative decrease in endocannabinoid anandamide and 2-AG concentrations    whereas visceral body fat exhibits an increase. Few studies have looked at cannabis effect on the weight of healthy subjects, and the results are conflicting. Cross-sectional observational studies are lower-quality studies that collect data at a single point in time.
One such study associated cannabis with greater fat mass,  but the others associated it with a smaller waist,  lower BMI,   and lower prevalence of obesity. Keep in mind, however, that those studies all relied on self-reported use, and that such reports are always, to some extent, unreliable. Studies that used more reliable methods paint a different picture. Three clinical trials whose participants were largely confined to a controlled hospital environment where food intake is controlled and accounted for saw increases in body weight.
Researchers have used endocannabinoid antagonists compounds that block CB1 to treat obesity caused by compulsive binging or irresistible cravings for sweets and snacks. Rats given the anti-obesity drug rimonabant, an endocannabinoid antagonist, lost weight and experienced a reduction in their blood levels of insulin. Yet in spite of these successes, rimonabant failed to earn approval from the U. Food and Drug Administration FDA and was withdrawn from the European market,  due to side effects that include nausea, dizziness, severe depression, and suicidal thoughts.
Since CB1s are found throughout the body, it is difficult to pinpoint the causes and mechanisms of these side effects. Still, in the future, safer endocannabinoid antagonists may play a role in treating obesity by blocking CB1 in order to increase adiponectin production and reduce appetite.
While many people wish they could lose weight, people with HIV-associated wasting syndrome, cancer-associated cachexia, or anorexia nervosa, notably, are often underweight. Two synthetic THC-based drugs have been developed to address the issue: This unintentional, steady weight loss associated with HIV can lead to poor health outcomes. Oral cannabinoids dronabinol may help increase weight but the results are not entirely conclusive. The loss of skeletal muscle associated with cancer is called cancer-associated cachexia, or simply cancer wasting.
People in the intervention groups gained, on average, 0. This increase is small, but it may still benefit this population. The inhibitory effect of marijuana on motor control may be attenuated in heavy users near daily , as a dose of mg marijuana 3. Acute inhalation of marijuana 1. Inhalation of marijuana tokes of 1. Interleukin 6 IL-6 is an inflammatory and immunostimulatory cytokine produced by the immune system which normally increases with age.
Usage of bhang in youth around 1. Activation of this receptor in B cells increases differentiation,  migration,  and activation  with at least one study also implicating this receptor in antibody class switching since incubation of B cells with cannabinoid agonists can increase immunoglobulin E IgE at the cost of IgM secretion in a manner blocked by CB2 antagonists. When investigating chronic marijuana smokers, baseline B cell count appeared to be lower than nonsmoking controls  lower baseline B cell count has also been noted in chronic bhang users relative to nonusers  but this was normalized over the course of 64 days with marijuana usage in hospitalized settings.
Many case studies have reported that heavy marijuana usage often precedes the development of gynecomastia breast tissue growth in males suggesting that marijuana may have intrinsic estrogenic properties that may disrupt normal hormonal balance in males.
A more recent study using in vitro as well as in vivo methods found that marijuana smoke condensate has an estrogenic effect that can be traced to phenolic compounds generated upon the combustion of plant materials. Thus, marijuana smoke may have intrinsic estrogenic properties that occur via estrogenic polyphenols, rather than cannabinoids as previously assumed. It has also been noted that Apigenin in Cannabis sativa is an estrogen antagonist at ,nM  while both formononetin  and 4,4,dihydroxymethoxybibenzyl from Cannabis sativa  are agonists.
Another study also found that while cannabinoids do not prevent gonadotropins from binding to receptors, they still lower testosterone by inhibiting cholesterol esterase, an enzyme needed for testosterone synthesis.
In humans, infusion of 10mg THC over 50 minutes as 0. Whereas the control group fluctuated at around 5. Two studies found that chronic users of marijuana did not display significantly different baseline levels of testosterone either gender, tested under non-smoking conditions up to daily smoking sessions, or 7 joints weekly.
It has been noted  that all human studies showing decreases are still within the normal biological range, suggesting that marijuana use is unlikely to influence behavior secondary to testosterone. Another possible mechnanism by which testosterone is depressed is through reducing hypothalamic and pituitary output of gonadotropin hormones, as administration of hCG Human chorionic gonadotropin in one study that noted marijuana-induced testosterone suppression also noted that the admistrration of hCG reversed it.
Marijuana use may suppress testosterone levels for up to 48 hours, as based on a mathematical simulation. Acute smoking of two 2.
Marijuana smoking causes an acute reduction Luteinizing Hormone LH levels in males. Chronic usage of marijuana, when tested under non-smoking conditions, is not associated with significant changes in follicle-stimulating hormone levels in men or women. One study found that inhalation of marijuana smoke from cigarettes containing 2. The magnitude of change noted with doses of marijuana corresponding to recreational use is not thought to be of a clinically relevant magnitude,  and there is no alteration in the diurnal rhythm of cortisol when comparing chronic users of marijuana to nonusers.
In contrast, lower doses have been found to have a mild stimulatory effect, suggesting that this mechanism may be subject to tolerance subchronically. The cannabinoid system plays several roles in the regulation and pathophysiology of the intestines, and marijuana and its constituents could theoretically play a role in aiding intestinal disorders by direct suppression of proinflammatory mediators, inhibition of intestinal motility and diarrhea, and attenuation of visceral sensitivity.
The effects of marijuana on intestinal disease in humans is limited but suggests that marijuana may be effective in reducing the symptoms of inflammatory bowel disease. Marijuana usage is thought to be a contributing factor in the development of nonalcoholic fatty liver disease NAFLD  as activation of the CB1 receptor in the liver hepatic tissue seems to promote lipogenesis in the liver  and CB2 receptors appear to be expressed in the NAFLD-affected liver but not healthy livers.
Mechanistically, when CB1 is activated in vitro the expression of the lipogenic factor SREBP-1c and the target enzymes ACC1 and fatty acid synthase FAS are increased  and injections of CB1 agonists causes lipogenesis in the liver of mice correlating with subsequent weight gain. Marijuana has effects on the lungs secondary to both the plant constituents but also due to the act of inhalation per se , since any combustable organic material regardless of its constituents inhaled may have a damaging effect on lung tissue.
The act of chronic marijuana inhalation has been associated with acute and chronic bronchitis as well as cases of cellular dysplasia, which are thought to be related to volatiles produced during combustion similar to tobacco-containing cigarettes. The state of marijuana tolerance assessed by surveying dependent adults is also associated with higher baseline sputum production in the morning, waking during the night with chest pains, wheezing outside of sickness , and exercise-induced shortness of breath were also increased in frequency relative to nonsmokers;  these effects were also noted in tobacco users, and hypothesized to be related to the inhalation of smoke per se.
However, a year follow-up as part of Coronary Artery Risk Development in Young Adults CARDIA study found that long-term marijuana use at low, common levels had a slight postive effect on pulmonary function measures; heavier users had an FEV1 measure no different from baseline, while FVC remained slightly improved even in heavy users, although data for very heavy users was sparse.
The decrease in IOP seen with marijuana peaks minutes after inhalation  although a decrease may occur before 30 minutes,  with these changes parallelling a decrease in peripheral blood pressure at a concenration which coincides with the psychoactive effects of marijuana.
The reduction in IOP has been noted in young adults who do not suffer from glaucoma as well. The testicles are known to express both CB1 and CB2 receptors in mice  and also express the fatty acid hydrolase FAAH enzyme of cannabinoid metabolism.
The cannabinoid system in cancer cells differs from normal cells; cancer cells often overexpress cannabinoid receptors, and the level of these receptors on cancer cells correlates with tumor agressiveness, which suggests that the cannabinoid system plays some role in cancer development. One mechanism by which cannabinoids may inhibit cancer cell growth is via inducing cell death through stimulation of the cannabinoid receptors on these cells, which stimulates the production of ceramide, in turn upregulating the stress-regulated protein known as p8, which ultimately leads to apoptosis.
An additional effect of cannabinoids seems to be to reduce the blood supply of tumors. Cannabinoid-induced, ceramide-dependent downregulation of vascular endotherlial growth factor VEGF and reduction in the stimulation of its receptor has been noted in gliomas. A third mechanism by which cannabinoids may inhibit cancer growth is by limiting its spread. When assessing rates of marijuana usage and lung cancer incidence survey research and investigating research that exludes tobacco usage, there was no increased risk for habitual frequent users relative to either nonhabitual infrequent or nonusers in regards to developing lung cancer.
A lack of association between marijuana usage and development of adenocarcinoma has been noted with marijuana usage despite a positive nonsignificant trend  although there may be some premalignant changes in the respiratory tract. A case-control study among head and neck cancer patients found no statistically significant association between marijuana smoking and head or neck cancer, even when restricting the analysis to those who never smoked tobacco and those who both never smoked tobacco and never drank alcohol both being additional risk factors for some head and neck cancers.
It should also be noted that, in cancerous prostate cells, activation of cannabinoid receptors decreases the protein expression of the androgen receptor and decreases the production and secretion of PSA  suggesting dual effects on the androgen receptor. In a large cohort study of older men aged , cannabis use was correlated with a lower risk of bladder cancer hazard ratio of 0.
A standardized high-cannabidiol Marijuana has been investigated for its usage in treating pain associated with chemotherapy,   although currently trials tend to be of relatively low quality based on a GRADE approach and are mostly conducted in chronic pain in general.
Marijuana is also reported to be used as adjuvant in chemotherapy for its appetite-stimulating effects, since weight loss from reduced food intake may worsen the prognosis of some cancers, and any attempt to circumvent weight loss is seen as protective,   although the clinical evidence supporting this specific use is relatively sparse.
The endocannabinoid system is involved in food and appetite regulation,  and has been shown to be involved in increasing lifespan under dietary restriction in a nematode model by reducing endogenous N-acylethanolamines NAEs signalling molecules that activate the endocannabinoid system. In transgenic mice possessing a mutated superoxide dismutase gene to model amyotrophic lateral sclerosis ALS , it has been noted that abolishing the FAAH enzyme fails to modify lifespan despite an increase in anandamide, however knocking out the CB1 receptor promotes increased lifespan.
The CB2 receptor is expressed in various immune cells  including microglia  The gene which expresses the CB2 receptor, CNR2, it may have its transcription upregulated during Alzheimer's disease relative to control,  which is correlated with cognitive impairment  resulting in more CB2 receptors demonstrated in vivo in humans  alongside a reduction in endogenous cannabinoid activity, thought to be due to upregulation of Fatty Acid Amide Hydrolase FAAH , which is an enzyme that breaks down endogenous cannabinoids such as anandaminde.
Marijuana has been investigated for the treatment of multiple sclerosis MS in part due to self-reports that it improves several physical and pain symptoms associated with MS.
In terms of the overall efficacy of marijuana in MS, a systematic review of the evidence to date by the American Academy of Neurology found that oral cannabis extract is effective in reducing spasticity and central pain or painful spasms in MS; smoked marijuana was of uncertain efficacy in both of the previous symptoms and marijuana overall was possibly or probably ineffective for other symptoms of MS.
Clinical trials have been performed to examine the effects of oral cannabis extract on MS. The cognitive effects of marijuana on patients with MS have also been examined.
In people with MS who report mostly daily marijuana smoking, following at least 12 hours cessation the smoking group appears to perform worse on tests of acute recall and working memory relative to those with MS who do not use marijuana;  fatigue and depression did not differ between groups. When looking at placebo-controlled trials the aforementioned studies being correlations , those with MS who took Cannabis sativa personally titrated to the optimal dose to reduce muscle spasticity for eight weeks at different times did not experience memory impairment with the former relative to placebo.
Amyotrophic Lateral Sclerosis ALS is a progressive neurological disorder in which glials cells may play a role, with human post-mortem evidence suggesting that spinal cord damage in this disorder is associated with CB2-positive microglial activity, suggesting that cannabinoids could in theory affect the progression of the disease.
Marijuana has been noted to have effects which may be beneficial in the treatment and palliation of ALS. Usage of marijuana recreationally is consistently correlated with various forms of mental illness, particularly psychosis,  but it is not entirely clear whether or not there exists a causal relationship; some reviews claim that more evidence exists for marijuana exacerbating existing schizophrenia rather than causing a "cannabis psychosis,"  while others suggest causation.
Because case-control studies may be prone to recall bias,  and since randomized controlled trials of medicinal marijuana use would not be applicable to populations which use the drug recreationally,  the best evidence for a causal link between marijuana use and symptoms of psychosis would be from longitudinal cohort studies.
Several such studies have been performed and seem to demonstrate a link between marijuana use and the development of psychotic symptoms. A follow-up to the first such study examining a large all-male cohort of Swedish conscripts found a dose-dependent increase in risk of developing schizophrenia in those who used marijuana without using other illicit substances OR 1.
A New Zealand sample also showed an positive association with dose-dependence between marijuana use and psychotic symptom development even after statistically taking into account symptoms previous to marijuana use, which ruled out pre-existing psychotic symptoms as the cause for marijuana use and other confounders.
In addition, early exposure to marijuana during adolescence seems to be associated to development of psychosis later in life. While the mechanisms of psychosis are not completely clear, it is biologically plausibile that marijuana may have a causative role in the development of psychosis and schizophrenic symptoms.
A second mechanism by which THC may induce psychotic symptoms may be through reducing glutamate activity. Starting in , hypoglutamatergic reduced glutamate neurotransmission has been implicated in schizophrenia,  specifically due to reduced activity of the NMDA receptor. Finally, there seems to exist a genetic mediator which predisposes adolescents who use marijuana to mediate the emergence of psychosis in some young users; specifically, a longitudinal study found that carriers of a variant of the catechol-O-methyltransferase COMT gene valine allele who used marijuana when young were more likely to develop schizophreniform disorder.
In survey of people with inflammatory bowel disease IBD found that those who used cannabis Small prospective trails have also shown some benefit. An uncontrolled pilot study involving 13 individuals showed self-reported improvement in patients with IBD receiving cannabis showed signficant improvements in several areas of well-being and a reduction in Harvey-Bradshaw index. Alcohol is a drug commonly used alongside marijuana, and both are known to interact with one another.
The dopamine-releasing effects of alcohol appear to be dependent on the CB1 receptor as blocking it can reduce dopamine activity induced by alcohol  and blocking this receptor has been noted to reduce voluntary alcohol intake in various rodent strains     likely due to the suppressive effect of blocking CB1 on dopamine release, since dopamine involved in the motivational effects in alcohol-seeking behaviors .
Tolerance to caffeine is known to increase density of adenosine A1 receptors in several brain regions,  and activation of this receptor is similar to activation of the CB1 receptor in the sense that they use are coupled to a similar pool of G-proteins  to subadditively suppress adenyl cyclase activity;  the mechanism for crosstolerance may exist downstream of the receptor-G-protein interface of the two signalling pathways.
A possible explanation for this may be linked back to glutamate, which is released from CB1 activation of astrocytes,  and its activation of glutaminergic signalling and subsequent downregulation and internalization of NMDA and AMPA receptors  via a COXdependent mechanism. NSAID drugs such as indomethacin, aspirin, and ibuprofen appear to be able to inhibit some of the neurological effects of marijuana, including the percieved 'high',   by inhibiting COX2, which is induced by CB1 receptor activation and leads to downregulation of glutamate receptors.
Nicotine is the main stimulatory component of cigarettes, and its signalling in the brain appears to interact with the main cannabinoid receptor CB1. It appears that activation of the CB1 receptor can potentiate the reinforcement stimulus for nicotine and lead to nicotine-seeking behavior in mice withdrawn from nicotine.
Reduction in CB1 receptor availability has been noted in numerous brain regions including the angular singulate cortex , the prefrontal cortex , and parahippocampal gyrus among others such as the parietal, posterior cingulate, and occipital cortices.
Withdrawal from marijuana exists but appears to differ from other drugs as it is not associated with any major medical or psychiatric problems that are seen with withdrawal from alcohol , benzodiazepines, or opioids; cannabis withdrawal tends to involve significant physical and mental impairments to well-being with risk of relapse. In terms of withdrawal symptoms' role in the risk of relapse, marijuana is comparable to tobacco in severity   although withdrawing from both simultaneously has been reported as being more severe than either alone.
Impared sleep is a commonly-reported symptom of marijuana withdrawal         and the intensity of this impairment is higher shortly after marijuana cessation gradually decreasing with time. The cluster of symptoms of nervousness, irritability, and anger are commonly reported with marijuana cessation.
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PDF | For more than a decade, medical marijuana has been at the forefront about those individuals using marijuana for medicinal purposes and the . race/ ethnicity, and gender between those included and excluded in the analysis sample. While Δ⁹-tetrahydrocannabinol (THC) has been widely studied in the realm. Marijuana is a drug used around the world due to its psychoactive properties. Additionally, nonpsychoactive components like CBD may have chronic benefits. are thought to have therapeutic uses in the realms that Δ9THC fails The Human Effect Matrix looks at human studies (it excludes animal and. Abstract: The use of medical cannabis in chronic illness is increasingly investigated, yet little is known While a reduction in seizure activity was observed in some children, included studies were poorly Key words: epilepsy; medical marijuana; paediatrics; risk assessment. Of these, 78 studies were excluded based.