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The occurrence of various degrees of GVHD was compared with historical data from patients, who had only received the standard treatment. This resulted in lower resistin levels compared to baseline. The hormone resistin is associated with obesity and insulin resistance. Compared to baseline, glucose-dependent insulinotropic peptide levels were elevated after CBD treatment.
This incretin hormone is produced in the proximal duodenum by K cells and has insulinotropic and pancreatic b cell preserving effects. CBD was well tolerated in the patients. However, with the comparatively low CBD concentrations used in this phasetrial, no overall improvement of glycemic control was observed.
When weight and appetite were measured as part of a measurement battery for side effects, results were inconclusive. For instance, the study mentioned above, where 23 children with Dravet syndrome were treated, increases as well as decreases in appetite and weight were observed as side effects. However, in the safety analysis group, consisting of subjects, 10 showed decreased weight and 12 had gained weight. Both these factors were not controlled for in the reviewed studies.
This review could substantiate and expand the findings of Bergamaschi et al. First, more studies researching CBD side effects after real chronic administration need to be conducted. Many so-called chronic administration studies, cited here were only a couple of weeks long.
Second, many trials were conducted with a small number of individuals only. To perform a throrough general safety evaluation, more individuals have to be recruited into future clinical trials. Third, several aspects of a toxicological evaluation of a compound such as genotoxicity studies and research evaluating CBD effect on hormones are still scarce. Especially, chronic studies on CBD effect on, for example, genotoxicity and the immune system are still missing.
Last, studies that evaluate whether CBD-drug interactions occur in clinical trials have to be performed. In conclusion, CBD safety profile is already established in a plethora of ways. However, some knowledge gaps detailed above should be closed by additional clinical trials to have a completely well-tested pharmaceutical compound. The study was commissioned by the European Industrial Hemp Association. EIHA paid nova-Institute for the review.
The MS Society claims the one in 10 sufferers of the condition whose pain and spasticity cannot be treated by medication available on the NHS should be able to take the drug without fear of prosecution. The society is calling for the first time for the 10, patients — one in 10 of the , people in Britain with MS — to be able to access cannabis without fear of arrest. It has changed its position after reviewing the evidence, consulting its medical advisers and seeking the views of 3, people who have the condition.
But there is sufficient evidence for our medical advisers to say that on the balance of probability, cannabis could benefit many people with MS experiencing pain and muscle spasms. Wales is the only home nation to provide the mouth spray through the NHS.
Norman Lamb, the Lib Dem health spokesman, said: This draconian law is potentially opening anything up to 10, MS sufferers to prosecution, and underlines why the Liberal Democrats have braved a tabloid backlash to campaign for the legalisation of cannabis. It is about time the government listened to the science.
Some are supportive while others are anxious about endorsing the use of a drug that can cause psychiatric problems.
The Royal College of GPs said it was currently drawing up policy on the issue and could not comment. The Royal College of Physicians, which represents hospital doctors, said it had no policy on the issue.
Dr Willy Notcutt, a pain management specialist at the James Paget hospital in Norfolk, who has been treating MS patients for more than 20 years, said: Many patients seek illegal cannabis to get help. Caroline Lucas, the Green party co-leader and its sole MP, said: By rigidly sticking to criminalising cannabis the government drives MS sufferers to illegally acquire the drugs, thus putting themselves as risk of prosecution simply for searching for pain relief. The Home Office said: Cannabis is controlled as a Class B drug under the Misuse of Drugs Act and, in its raw form, currently has no recognised medicinal benefits in the UK.
Imagine running a marathon while sharp pain darts up and down your legs. This is what multiple sclerosis feel like for me.
But three years ago I was offered a treatment that could help. The results were incredible. My muscle tension eased and I started to feel my legs moving better. I could exercise without getting as tired as quickly. For the first time in a long time I felt that I was managing my condition. I have been forced to pay for this drug myself. I take Sativex but other people get similar relief from cannabis in its pure form.
But for those it helps, it should be made legal. I know there will never be a cure, but I am just looking for a way to make things easier. Now I have been presented with something that offers me hope and the NHS say they cannot afford it. Sadly, ill people have been and are being exploited by the drug legalisation lobby, in furtherance of their nirvana of recreational cannabis for all.
Cannabis is a very harmful psychoactive drug, it induces dependency in around 1 in 9 or 10 users. It has numerous bad effects. Smoking is obviously not a sensible delivery system for medication, yet a lot of those complaining want to smoke cannabis.
Cannabis based drugs like Sativex are in the pharmacopeia thanks to the wise licensing of the research on them by successive UK governments. They must show efficacy and they must satisfy NICE. There are no grounds at all for making cannabis any sort of special case, in fact the recreational user base and the legalisation lobby distort the arguments and would be better remaining silent.
Colorado legalized the commercialization of medical marijuana in and recreational marijuana use in They found that the annual number of visits with a cannabis related diagnostic code or positive for marijuana from a urine drug screen more than quadrupled during the decade, from in to in More than half also had positive urine drug screen tests for other drugs. Ethanol, amphetamines, benzodiazepines, opiates and cocaine were the most commonly detected.
Based on the findings of his study, however, he said he suspects these national surveys do not entirely reflect the effect legalization may be having on teen usage. Numbers in this news release reflect updated information provided by the researchers.
The abstract is available at https: This international gathering includes paediatric researchers, leaders in academic paediatrics, experts in child health, and practitioners. The PAS Meeting is produced through a partnership of four organizations leading the advancement of paediatric research and child advocacy: For more information, visit the PAS Meeting online at www.
For additional AAP News coverage, visit http: How do you know when you are being softened up for something? One sure sign is when what you are being asked to give your support to is sold to you as entirely unproblematic or as a panacea to a host of problems. What could be wrong with that, I hear you ask.
Well, if I was sceptical about the stated purpose of this report when it was first published, I am even more so this time. First, because the case for medicinal cannabis is based on a false premise, which the recent licensing of cannabidiol demonstrates again.
And third, there no safe way of using the unprocessed plant for recreational let alone medical purposes. Two approved cannabis-derived medications, Marinol and Sativex, exist already and a third, Epidiolex is undergoing clinical trials at the moment.
Evidence of the efficacy of the derived compounds of cannabis for the wide range of symptoms they have been tested on is at best weak. Who is their right mind would chose mould over an approved antibiotic? And where is the luminary who thinks smoking is a sensible medication delivery system?
They have really been doing rather well at convincing the media of their non-existent problem. No wonder Baroness Meacher, chair of the aforesaid APPG, sounded so triumphant on the airwaves yesterday as she pushed the case for medipot to an all believing radio host. Even the Mail all that has stood between us and drugs legalisation, she as much as said had finally written a balanced article on the topic, she crowed.
She herself certainly was not balanced. Running true to form, Baroness Meacher failed in her interview go to circa one hour, 6 minutes into the programme to either mention the medicines approval system or the recent licensing of cannabidiol as a medicine. In fact, the opposite is the case, as drugs policy analyst David Raynes made clear on the same programme. The UK government broke ground when it licensed research into cannabis in There we had it. According to the Washington Times Source: No wonder so many capitulated.
And more in the last three years. More recently he revealed that he was not too keen on cannabis compounds being subjected to scientific drug research trials. I wonder if this too is why Meacher is so reluctant to give a full account of cannabis research and medical regulation? It rather pulls her medi-pot carpet from under her feet.
As part of the ongoing efforts of the International Narcotics Control Board INCB to raise awareness of key issues relevant to international drug control, I have the pleasure to share with you three short texts:.
Carrying by international travellers of small quantities of preparations containing narcotic drugs and psychotropic substances for personal medical use. INCB is the independent, quasi-judicial body charged with promoting and monitoring Government compliance with the three international drug control conventions: I totally agree that we all need to let Attorney General Jeff Sessions know that the majority of Americans suffer because of marijuana ….
It is a factor in crime, physical and mental health, academic failure, lost productivity, et al. American cannot be great again if we continue to allow poison to be grown and distributed to the masses.
That obviously would not be for personal use. We would just have thousands of new drug dealers, with more crime, more child endangerment, more BHO labs blowing up, more traffic deaths, et al. GW Pharmaceuticals plc Nasdaq: GBM is a particularly aggressive brain tumour, with a poor prognosis.
CBD in the treatment of glioma. Median survival for the THC: CBD group was greater than days compared with days in the placebo group. CBD was generally well tolerated with treatment emergent adverse events leading to discontinuation in two patients in each group. The results of some biomarker analyses are still awaited. These promising results are of particular interest as the pharmacology of the THC: CBD product appears to be distinct from existing oncology medications and may offer a unique and possibly synergistic option for future glioma treatment.
We believe that the signals of efficacy demonstrated in this study further reinforce the potential role of cannabinoids in the field of oncology and provide GW with the prospect of a new and distinct cannabinoid product candidate in the treatment of glioma.
The study, designed to evaluate a number of safety and efficacy endpoints, comprised an initial phase where the safety of THC: CBD in combination with dose-intense temozolomide an oral alkylating agent that is a standard first-line treatment for GBM was assessed in 2 cohorts of 3 patients each. Following a satisfactory independent safety evaluation, the study then entered a randomized placebo-controlled phase where 12 patients were randomized to THC: CBD as add-on therapy compared with 9 patients randomized to placebo plus standard of care.
Beginning in and prior to initiating this study, GW conducted substantial pre-clinical oncologic research on several cannabinoids in various forms of cancer including brain,. These studies have resulted in approximately 15 publications and show the multi-modal effects of cannabinoids on a number of the key pathways associated with tumour growth and progression. The combination of THC and CBD showed good efficacy in various animal models of glioma, particularly when used in combination with temozolomide.
Initial in vitro studies showed that the combined administration of THC and CBD led to a synergistic reduction in the viability of U87MG glioma cells when compared to the administration of each cannabinoid individually. The co-administration of temozolomide with THC and CBD had further synergistic effects, causing a significant reduction in cell viability.
These pre-clinical studies justified the initiation of the Phase 2 clinical study. This portfolio is designed to protect the use of various cannabinoids individually or in combination, in the treatment of a variety of oncology-specific disorders and product formulations. Gliomas are tumours that arise from glial cells mainly in the brain but can also be found within the spinal cord.
Within the category of Glioma there are multiple different tumor types. GBM is the most common Glioma and is one of the most common primary brain tumors, accounting for They are also the most aggressive with only Studies of patients with high-grade gliomas showed that headache was the most common initial presenting symptom. These headaches can be persistent lasting more than six months and are often associated with other symptoms, including seizures, visual disturbances, cognitive impairment and nausea and vomiting depending on the location and growth rate of the tumor.
Founded in , GW is a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform in a broad range of disease areas. The Company has a deep pipeline of additional cannabinoid product candidates which includes compounds in Phase 1 and 2 trials for glioma, schizophrenia and epilepsy.
For further information, please visit www. Currently, 29 states and Washington, DC, have passed laws to legalize medical marijuana. Although evidence for the effectiveness of marijuana or its extracts for most medical indications is limited and in many cases completely lacking, there are a handful of exceptions.
For example, there is increasing evidence for the efficacy of marijuana in treating some forms of pain and spasticity, and 2 cannabinoid medications dronabinol and nabilone are approved by the US Food and Drug Administration for alleviating nausea induced by cancer chemotherapy. A systematic review and meta-analysis by Whiting et al1 found evidence, although of low quality, for the effectiveness of cannabinoid drugs in the latter indication.
The anti -nausea effects of tetrahydrocannabinol THC , the main psychoactive ingredient in marijuana, are mediated by the interactions of THC with type cannabinoid CB1 receptors in the dorsal vagal complex. Cannabidiol, another cannabinoid in marijuana, exerts antiemetic properties through other mechanisms. Nausea is a medically approved indication for marijuana in all states where medical use of this drug has been legalized.
However, some sources on the internet are touting marijuana as a solution for the nausea that commonly accompanies pregnancy, including the severe condition hyperemesis gravidarum. Although research on the prevalence of marijuana use by pregnant women is limited, some data suggest that this population is turning to marijuana for its antiemetic properties, particularly during the first trimester of pregnancy, which is the period of greatest risk for the deleterious effects of drug exposure to the foetus.
Marijuana is the most widely used illicit drug during pregnancy, and its use is increasing. In addition, an analysis of pregnancy data from Hawaii reported that women with severe nausea during pregnancy, compared with other pregnant women, were significantly more likely to use marijuana 3. Although the evidence for the effects of marijuana on human prenatal development is limited at this point, research does suggest that there is cause for concern.
A recent review and a meta-analysis found that infants of women who used marijuana during pregnancy were more likely to be anaemic, have lower birth weight, and require placement in neonatal intensive care than infants of mothers who did not use marijuana.
Studies have also shown links between prenatal marijuana exposure and impaired higher-order executive functions such as impulse control, visual memory, and attention during the school years. The potential for marijuana to interfere with neurodevelopment has substantial theoretical justification.
The endocannabinoid system is present from the beginning of central nervous system development, around day 16 of human gestation, and is increasingly thought to play a significant role in the proper formation of neural circuitry early in brain development, including the genesis and migration of neurons, the outgrowth of their axons and dendrites, and axonal pathfinding. Substances that interfere with this system could affect foetal brain growth and structural and functional neurodevelopment.
An ongoing prospective study, for example, found an association between prenatal cannabis exposure and foetal growth restriction during pregnancy and increased frontal cortical thickness among school-aged children. A recent study in mice found brain abnormalities, eye deformations, and facial disfigurement cleft palate in mouse foetuses exposed at day 8 of gestation to a potent full cannabinoid agonist, CP, The percentage of mouse foetuses with birth defects increased in a linear fashion with dose.
The eighth day of mouse gestation is roughly equivalent to the third or fourth week of embryonic development in humans, which is before many mothers know they are pregnant. It is unknown whether these kinds of effects translate to humans; thus far, use of synthetic cannabinoids has not been linked to human birth defects, although use of these substances is still relatively new.
Marijuana is also being used in new ways that have the potential to expose the user to much higher THC concentrations—such as the practice of using concentrated extracts eg, hash oil. More research is needed to clarify the neurodevelopmental effects of prenatal exposure to marijuana, especially high-potency formulations, and synthetic cannabinoids. In women who use drugs during pregnancy, there are often other confounding variables related to nutrition, prenatal care, and failure to disclose substance use because of concerns about adverse legal consequences.
Even with the current level of uncertainty about the influence of marijuana on human neurodevelopment, physicians and other health care providers in a position to recommend medical marijuana must be mindful of the possible risks and err on the side of caution by not recommending this drug for patients who are pregnant. Although no states specifically list pregnancy-related conditions among the allowed recommendations for medical marijuana, neither do any states currently prohibit or include warnings about the possible harms of marijuana to the foetus when the drug is used during pregnancy.
Only 1 state, Connecticut, currently includes an exception to the medical marijuana exemption in cases in which medical marijuana use could harm another individual, although potential harm to a foetus is not specifically listed. In , the American College of Obstetricians and Gynecologists issued a committee opinion discouraging physicians from suggesting use of marijuana during preconception, pregnancy, and lactation.
Pregnant women and those considering becoming pregnant should be advised to avoid using marijuana or other cannabinoids either recreationally or to treat their nausea. An evaluation of risk applied to marijuana products for medical purposes concludes that advanced mitigation strategies and new protective delivery protocols are necessary to adequately protect the public from harm.
There are a number of medications that fall into existing REMS restrictions include thalidomide, clozapine, isotretinoin, and lenilidomide. In both of these programs only prescribers and pharmacists who are registered or patients who are enrolled and who have agreed to meet all the conditions of the program are given access to these drugs. They all lack the pesticides, herbicides and fungicides placed on marijuana plants during growth. The longest approved agents, dronabinol and nabilone are indicated for short term use in nausea and vomiting due to chemotherapy and appetite stimulation.
Although thalidomide was withdrawn from the market in West Germany and the UK by December 2, , it remained legally available in Canada until March of It was still available in some Canadian pharmacies until mid-May of A trial conducted in Germany against Gruenenthal, for causing intentional and negligent bodily injury and death, began in ending in with a claim of insufficient evidence.
Later, the victims and Gruenenthal settled the case for million dollars. In the American pharmaceutical laws were increased by the Kefauver-Harris Drug Amendment of and proof for the therapeutic efficiency through suitable and controlled studies would be required for any government approved medication.
In , the Ministry of National Health and Welfare the current Health Canada awarded Canadian-born thalidomide survivors a small lump-sum payment. Negotiations with the drug companies failed. The Canadian taxpayer alone paid to amend the survivors by way of monetary award. It is an immunomodulatory drug and today, it is used mainly as a treatment of certain cancers multiple myeloma and leprosy.
When exposure occurs in utero, there is an association with many congenital abnormalities including cardiac septal defects, anotia, anophthalmos, and gastroschisis. Marijuana use can disrupt foetal growth and the development of organs and limbs and may result in mutagenic alterations in DNA. Cannabis has also been associated with foetal abnormalities in many studies including low birth weight, foetal growth restriction, preterm birth spontaneous miscarriage, spina bifida and others.
Phocomelia has been shown in testing in a similar preclinical model hamster to that which revealed the teratogenicity of thalidomide. THC has the ability to interfere with the first stages in the formation of the brain of the fetus; this event occurs two weeks after conception. The existence of specific health risks associated with marijuana products are acknowledged by national and various local governments and a plethora of elected officials in both Canada and the United States.
Warnings and the contraindications for use by specific populations and in association with identified conditions, have been publicized by the Federal Government of Canada and the Federal Government of the United States of America through their respective health agencies.
A government of Canada leaflet produced by Health Canada and updated in December Consumer Information — Cannabis Marihuana, marijuana reads Studies supporting the safety and efficacy of cannabis for therapeutic purposes are limited and do not meet the standard required by the Food and Drug Regulations for marketed drugs in Canada.
This can affect your motor skills, including your ability to drive. It can also increase anxiety and cause panic attacks, and in some cases cause paranoia and hallucinations. Negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy. In Canada, the College of Family Physicians has issued guidelines for issuing marijuana prescriptions. In February The College of Family Physicians of Canada issued a statement advancing the position that physicians should sign a declaration rather than write a prescription as the potential liability, as well as the ethical obligations, for health professionals prescribing marijuana for medical purposes appears not to have been adequately addressed by Health Canada.
If the patient suffers a cannabis-related harm, physicians can be held liable, just as they are with other prescribed medications. Physicians cannot be expected to prescribe a drug without the safeguards in place as for other medications — solid evidence supporting the effectiveness and safety of the medication, and a clear set of indications, dosing guidelines and precautions.
Mental health experts and scientists joined high-ranking government officials to discuss an emerging body of research that identified clear links between marijuana use and mental health disorders, including depression, suicidal thoughts and schizophrenia. In the Obama Administration steadfastly opposes legalization of marijuana and other drugs because legalization would increase the availability and use of illicit drugs, and pose significant health and safety risks to all Americans, particularly young people.
The dispensing of marijuana for medical purposes must follow a strict dispensing and monitoring protocol; no less arduous than that used for the delivery of drugs such as thalidomide. The first order for a government is to protect the public.
As such, it befits a government approving marijuana for medical purposes to implement a REMS program. Failure to comply with the REMSMP program will result in fines and other appropriate penalties to the marijuana dispensaries. Pregnancy must be prevented by both the male and female patients during marijuana treatment by the use of two reliable methods of contraception.
Must avoid pregnancy for at least 4 weeks before beginning marijuana therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit to either abstain continuously from heterosexual intercourse or use two methods or reliable birth control as mentioned.
They must have two negative pregnancy tests prior to initiating marijuana therapy and monthly pregnancy test with normal menses or two months with abnormal menses and for at least 1 month after stopping marijuana therapy. DNA damage from marijuana is present in the semen of patients receiving marijuana. Male patients using marijuana may not donate sperm. Patients must not donate blood during treatment with marijuana and for at least 1 month following discontinuation of marijuana because the blood might be given to a pregnant female patient whose fetus should not be exposed to marijuana.
Females of reproductive potential should avoid contact with marijuana through cutaneous absorption, smoke inhalation or orally. Appropriate universal precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to marijuana. Nursing mothers must not be receiving marijuana. Male patients must perform weekly testicular self-evaluations while receiving marijuana. They are also required to have their primary care provider perform a testicular evaluation and a HCG blood test performed every 4 months while receiving marijuana.
The presence of these mental health disorders must be evaluated by a licensed psychiatrist or psychologist by use of the Mini International Neuropsychiatric Interview or equivalent validated diagnostic instrument before marijuana is started. The diagnostic mental health evaluation tool will be completed every 1month by an independent licensed psychiatrist or psychologist for a minimum of 6 months until unchanging and then every 4 months thereafter while receiving marijuana ending 4 months after the last exposure to marijuana.
History of Substance Abuse Disorder: As the prevalence of substance use disorders amongst those patients requesting medical authorization of marijuana products is known to be extremely high the patient population must be screened prior to dispensing marijuana products for risk of a substance use disorder. We believe that the same will happen for marijuana products and that it is our responsibility to assist the Canadian government to protect the public from a similar outcome.
The REMSMP program described assists in providing patient education, provider education and required patient monitoring before any marijuana products are allowed to be dispensed. The program also requires on-going data collection and analysis, to determine the actual hazards from marijuana use and whether the program should even continue.
Orens A, et al. Marijuana Equivalency in Portion and Dosage. An assessment of physical and pharmacokinetic relationships in marijuana production and consumption in Colorado.
Prepared for the Colorado Department of Revenue. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. College of Family Physicians of Canada. College of Family Physicians of Canada; Lacson JCA, et al. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk.
Daling JR, et al. Association of marijuana use and the incidence of testicular germ cell tumors. Gurney J, et al. Cannabis exposure and risk of testicular cancer: Takizawa A, et al. Moore TH, et al. Cannabis use and risk of psychotic or affective mental health outcomes: Large M, et al. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand, ; The acute effects of cannabinoids on memory in humans: Sheehan D, et al. Currently 25 states and the District of Columbia have medical cannabis programs.
We have no political position on cannabis legalization. We study the cannabis plant, also known as marijuana, and its related chemical compounds. Despite claims that cannabis or its extracts relieve all sorts of maladies, the research has been sparse and the results mixed. What does the available research suggest about medical cannabis, and why do we know so little about it? While some researchers are investigating smoked or vaporized cannabis most are looking at specific cannabis compounds, called cannabinoids.
THC is the main active component of cannabis. They are prescribed to increase appetite and prevent wasting caused by cancer or AIDS. Seventeen states have passed laws allowing access to CBD for people with certain medical conditions. Our bodies also produce cannabinoids, called endocannabinoids. Researchers are creating new drugs that alter their function, to better understand how cannabinoid receptors work.
Cannabis is promoted as a treatment for many medical conditions. Is it a chronic pain treatment? Research suggests that some people with chronic pain self-medicate with cannabis. However, there is limited human research on whether cannabis or cannabinoids effectively reduce chronic pain.
Research in people suggest that certain conditions, such as chronic pain caused by nerve injury, may respond to smoked or vaporized cannabis, as well as an FDA-approved THC drug.
But, most of these studies rely on subjective self-reported pain ratings, a significant limitation. An alternative research approach focuses on drug combination therapies, where an experimental cannabinoid drug is combined with an existing drug. For instance, a recent study in mice combined a low dose of a THC-like drug with an aspirin-like drug. The combination blocked nerve-related pain better than either drug alone. In theory, the advantage to combination drug therapies is that less of each drug is needed, and side effects are reduced.
In addition, some people may respond better to one drug ingredient than the other, so the drug combination may work for more people. Similar studies have not yet been run in people. Well-designed epilepsy studies are badly needed Despite some sensational news stories and widespread speculation on the internet, the use of cannabis to reduce epileptic seizures is supported more by research in rodents than in people.
In people the evidence is much less clear. There are many anecdotes and surveys about the positive effects of cannabis flowers or extracts for treating epilepsy. While CBD has gained interest as a potential treatment for seizures in people, the physiological link between the two is unknown. As with chronic pain, the few clinical studies have been done included very few patients. Studies of larger groups of people can tell us whether only some patients respond positively to CBD. We also need to know more about the cannabinoid receptors in the brain and body, what systems they regulate, and how they could be influenced by CBD.
For instance, CBD may interact with anti-epileptic drugs in ways we are still learning about. It may also have different effects in a developing brain than. Caution is particularly urged when seeking to medicate children with CBD or cannabis products. Well-designed studies are the most effective way for us to understand what medical benefits cannabis may have. But research on cannabis or cannabinoids is particularly difficult.
In order to study cannabis, a researcher must first request permission at the state and federal level. This is followed by a lengthy federal review process involving inspections to ensure high security and detailed record-keeping. In our labs, even the very small amounts of cannabinoids we need to conduct research in mice are highly scrutinized.
This regulatory burden discourages many researchers. Designing studies can also be a challenge. Bias is a limitation of any study that includes self-reports. These studies are also limited by using whole cannabis, which contains many cannabinoids, most of which are poorly understood. Placebo trials can be a challenge because the euphoria associated with cannabis makes it easy to identify, especially at high THC doses. People know when they are high.
Another type of bias, called expectancy bias, is a particular issue with cannabis research. This is the idea that we tend to experience what we expect, based on our previous knowledge. For example, people report feeling more alert after drinking what they are told is regular coffee, even if it is actually decaffeinated.
Similarly, research participants may report pain relief after ingesting cannabis, because they believe that cannabis relieves pain. The best way to overcome expectancy effects is with a balanced placebo design, in which participants are told that they are taking a placebo or varying cannabis dose, regardless of what they actually receive.
Studies should also include objective, biological measures, such as blood levels of THC or CBD, or physiological and sensory measures routinely used in other areas of biomedical research. At the moment, few do this, prioritizing self-reported measures instead. Abuse potential is a concern with any drug that affects the brain, and cannabinoids are no exception.
Cannabis is somewhat similar to tobacco, in that some people have great difficulty quitting. And like tobacco, cannabis is a natural product that has been selectively bred to have strong effects on the brain and is not without risk.
Although many cannabis users are able to stop using the drug without problem, percent of users have difficulty quitting. Repeated use, despite the desire to decrease or stop using, is known as cannabis use disorder. As more states more states pass medical cannabis or recreational cannabis laws, the number of people with some degree of cannabis use disorder is also likely to increase.
It is too soon to say for certain that the potential benefits of cannabis outweigh the risks. But with restrictions to cannabis and cannabidiol loosening at the state level, research is badly needed to get the facts in order.
The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. However, it is critical that societal passions not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure.
This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure, and is combined with an illustration of the neuropathological findings in a fatal case of cannabis-induced psychosis. The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound.
Contrary to popular perception, there is little objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if sub-sets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis.
Making physicians the gatekeepers of legal marijuana is not fair to doctors and is not conducive to public health. The problem is that marijuana has been prescribed by the courts, not by health-care professionals.
They included impairments in attention, increased anxieties, psychosis and cancer. Physicians are facing a deluge of requests to prescribe cannabis, and guidelines will give them the support they need to refuse to prescribe cannabis when medically unnecessary or unsafe. Because Health Canada allows marijuana to be prescribed by physicians, that enhances the public perception that marijuana is not only harmless, but therapeutic.
It uses solid evidence and rigorous scientific research, and it has saved lives. Marijuana should undergo the same scrutiny as to its potential benefits and harms. But medical marijuana is not treated the same as other drugs. Science has little to do with it. If marijuana can relieve the agony of someone with severe chronic pain or terminal cancer, who would withhold it? It should be handled the same, with regulations as to its production and distribution.
We should not clog our courts and jails with pot-smokers. Authoritative organisations which do not support smoked pot or edibles as a legitimate form of medication, listed by: American Medical Association ,. American Cancer Society ,. National Multiple Sclerosis Society,. American Academy of Pediatrics,. American Academy of Ophthalmology ,. American Society of Addiction Medicine ,. Marcel O Bonn-Miller Marcel. For all author emails, please log on.
The electronic version of this article is the complete one and can be found online at: The present investigation aimed to provide an objective narrative review of the existing literature pertaining to the benefits and harms of marijuana use for the treatment of the most common medical and psychological conditions for which it has been allowed at the state level. Common medical conditions for which marijuana is allowed i.
Post-traumatic stress disorder was also included in the review, as it is the sole psychological disorder for which medical marijuana has been allowed. Findings indicate that, for the majority of these conditions, there is insufficient evidence to support the recommendation of medical marijuana at this time. A significant amount of rigorous research is needed to definitively ascertain the potential implications of marijuana for these conditions.
It is important for such work to not only examine the effects of smoked marijuana preparations, but also to compare its safety, tolerability, and efficacy in relation to existing pharmacological treatments. National estimates suggest that 5. This represents an increase of approximately Similar increases have also been noted among vulnerable populations in the U.
Marijuana is currently illegal in every country in the world. In , Uruguay voted to legalize state-controlled marijuana sales but implementation of the law has been postponed until The policy in the Netherlands is mixed, with permissible retail sale of marijuana at coffee shops, but restrictions on production and possession. Like the Netherlands, the United States currently has a mixed drug policy; marijuana is an illegal Schedule I drug under U. However, marijuana policies vary by state, with some states e.
Furthermore, as of this review, 23 states and the District of Columbia have passed legislation allowing medical marijuana i. Though some recent work has reviewed the adverse effects of marijuana [ 4 ] or the efficacy of marijuana for certain conditions e. The list of all conditions for which medical marijuana is allowed, according to the legislation of each U.
From this list, common conditions for which medical marijuana is allowed i. Though not presently a qualifying condition in at least 80 percent of states with medical marijuana laws, PTSD was also included in the review, as it is rapidly gaining attention and recognition as the sole psychological disorder for which medical marijuana is allowed.
Studies for this narrative review were included based on a literature search in the following databases: Within each database, each combination of the following key marijuana terms and the above-listed conditions were used to conduct a search: References within each obtained article were also examined to assure that no studies were overlooked. Only published, English-language studies were included in this review. Though the primary focus of this review is on studies of marijuana plant effects, as these are most relevant to recent medical marijuana legislation, synthetic or plant-derived cannabinoids e.
Indeed, for purposes of the review, references to oral administrations of marijuana constitute a pharmaceutical grade extraction administered in tablet or liquid form e.
Finally, the present review is organized alphabetically by condition for which marijuana is allowed, rather than in order of disorder for which it is most to least commonly recommended, or strength of the evidence. We chose this approach as there is currently only state-level data [ 7 ]-[ 9 ], rather than national, representative data on the primary conditions for which medical marijuana is used or recommended, and the existing literature and state of the evidence for many conditions remains relatively poor.
AD, the leading form of dementia in the elderly, is a progressive, age-related disorder characterized by cognitive and memory deterioration [ 10 ].
AD has several neuropathological markers, including neuritic plaques and neurofibrillary tangles [ 11 ]. Although several researchers have suggested dronabinol and Nabilone may act on these mechanisms to confer therapeutic effects for patients with AD [ 12 ],[ 13 ], a recent Cochrane systematic review found no evidence that dronabinol was effective in reducing symptoms of dementia [ 14 ].
The authors of a placebo-controlled crossover study of 15 patients with AD who were refusing to eat suggest that dronabinol increases weight gain and decreases disturbed behavior [ 15 ], but there is insufficient quantitative data to support this conclusion [ 14 ], and one study participant had a grand mal seizure following dronabinol administration [ 15 ].
Another pilot study of two patients with dementia found that dronabinol reduced nocturnal motor activity [ 16 ]. No studies have examined the effects of smoked marijuana in patients with AD. In sum, there is insufficient evidence to recommend marijuana for the treatment of AD.
Future directions should include conducting randomized controlled trials RCTs comparing both smoked and oral marijuana to placebo and existing treatments, with sample sizes large enough to detect treatment effects and the safety and tolerability of marijuana.
ALS is a fatal neurological disease with symptoms that include weakness, spasticity, and respiratory difficulties. Cannabinoids are hypothesized to act in the regions of established pathophysiology for ALS [ 17 ] and could be used for symptom management e. Although there is limited evidence from a survey of patients with ALS that marijuana consumed in a variety of forms i.
These survey findings indicate that up to 10 percent of patients use marijuana for symptom management, and these self-reports suggest efficacy in increasing appetite and mood and decreasing pain, spasticity, and drooling. However, as is consistent with the half-life of smoked marijuana, the beneficial effects of marijuana on symptoms of ALS were fewer than 3 hours in duration [ 19 ]. There is currently insufficient clinical evidence in humans with ALS to recommend cannabinoids as primary or adjunctive therapy.
In patients with HIV or cancer, smoked marijuana and dronabinol have been shown to increase weight gain [ 21 ],[ 22 ] and food intake [ 22 ],[ 23 ] compared to placebo. In a within-subject, double-blind, staggered, double-dummy study of nine individuals with muscle mass loss, dronabinol resulted in significantly greater calorie consumption than smoked marijuana [ 24 ].
A within-subject, double-blind, placebo-controlled trial with seven HIV-positive marijuana smokers taking antiretroviral medications found that compared to placebo, dronabinol increased caloric intake [ 25 ]. Additional studies indicate that dronabinol administration increases appetite, decreases nausea, and protects against weight loss [ 26 ], with effects on appetite and weight stability enduring in long-term follow-up [ 27 ].
Both dronabinol and smoked marijuana increase the number of eating occasions [ 22 ],[ 25 ], and smoked marijuana may also affect weight gain and calorie intake by modulating appetite hormones [ 28 ].
These studies demonstrate that marijuana has positive effects on cachexia resulting from a medical condition, but are largely limited by small sample sizes. Cancer is a qualifying medical condition in every state that has approved marijuana for medical use [ 30 ]. The majority of clinical research examining the relation between THC and cancer has evaluated the effect of smoked THC on the risk for cancer, or the palliative effects of THC on chemotherapy-related nausea and emesis, chronic pain, and wasting reviewed in respective sections ; few studies have studied the effect of marijuana in any form on the treatment of primary cancer pathology.
In vitro and in vivo research suggests that cannabinoids inhibit tumor growth [ 30 ] via several proposed mechanisms e. The only clinical trial of THC on cancer examined intracranial administration of THC to nine patients with recurrent glioblastoma multiforme who had failed surgical- and radiotherapy, and results indicated that THC decreased tumor growth, while being well-tolerated with few psychotropic effects [ 33 ]. This study is limited by lack of generalizability, and clinical trials with larger representative samples that examine oral or smoked administration of THC are essential to elucidate the effects on cancer pathology.
There is currently insufficient evidence to recommend marijuana for the treatment of cancer, but there may be secondary treatment effects on appetite and pain.
CD is an inflammatory bowel disease IBD that has no cure; treatment targets include reducing inflammation and secondary symptoms. Between 16 percent and 50 percent of patients use marijuana to relieve symptoms of IBD [ 34 ]-[ 36 ], and patients using marijuana for 6 months or longer are five times more likely to have had surgery for their IBD [ 34 ]; whether marijuana exacerbates disease progression or more severe disease results in self-medication is unclear.
Only one placebo-controlled study of the effects of marijuana in patients with CD has been conducted[ 37 ]. This study found that there was no difference between placebo and smoked marijuana on CD remission defined as a CD Activity Index CDAI of less than , and that marijuana was superior to placebo in promoting clinical response a decrease in CDAI score greater than , reducing steroid use, and improving sleep and appetite [ 37 ].
Importantly, this study did not include objective measurement of inflammatory activity, and there was no significant difference in placebo and treatment groups 2 weeks after treatment cessation [ 37 ]. Until clinical trials with objective measurement of treatment effects over an extended period of time are conducted to examine the safety and efficacy of marijuana for the treatment of IBD, there is insufficient evidence for the use of marijuana for the treatment of IBD.
The known effects of cannabinoids on epilepsy and seizures are largely from animal studies, surveys, and case studies. Several animal studies indicate that marijuana and its constituents exhibit anticonvulsant effects [ 38 ]-[ 41 ] and reduce seizure-related mortality [ 39 ], but there is also evidence that cannabinoids can lower the threshold for seizures [ 42 ], and THC withdrawal increases susceptibility for convulsions [ 42 ].
Cross-sectional surveys indicate that 16—21 percent of patients with epilepsy smoke marijuana [ 43 ],[ 44 ], with some reporting positive effects e. Based on a Cochrane review, the few RCTs that have been conducted in humans include a total of 48 participants [ 45 ] and only examine treatment with cannabidiol.
These trials exhibited heterogeneity of effects: In addition, none of the studies examined response at greater than 6-month follow-up [ 45 ]. Systematic reviews of the literature have concluded that there is insufficient clinical data to support or refute the use of cannabinoids for the treatment of epilepsy and seizures [ 5 ],[ 45 ].
Glaucoma is a neurodegenerative eye disease that can cause blindness by damaging retinal ganglion cells and axons of the optic nerve. Intraocular pressure IOP can influence both onset and progression of glaucoma and is often a target for intervention. Small samples have demonstrated reduced IOP following smoked marijuana [ 49 ],[ 50 ], but the effect is only present in 60—65 percent of individuals [ 51 ] and lasts for 3—4 hours, requiring repeated dosing throughout the day [ 52 ].
Furthermore, patients discontinue marijuana use due to side effects e. Development of eye drops for topical application of THC would minimize psychoactive and other side effects but is complicated by the high lipophilicity and low water solubility of cannabinoids [ 52 ],[ 56 ].
Additionally, the distance from the application site to the retina may be too great to afford neuroprotective benefits [ 52 ], given that only 5 percent of an applied dose penetrates the cornea to the intraocular space [ 56 ]. Of the studies that have been conducted, one longitudinal study demonstrates that smoked marijuana has no effect on HCV progression in individuals with HIV [ 57 ].
In contrast, individuals with HCV who smoke marijuana have a higher fibrosis progression rate [ 58 ] and more severe steatosis [ 59 ], with daily smokers having a more rapid rate of progression and greater severity [ 60 ] than occasional marijuana users [ 58 ],[ 59 ].
Marijuana may have independent negative effects on steatosis [ 59 ], but because none of these findings were in the context of a clinical trial, these correlations are not causal and it is possible that individuals who use marijuana do so to manage greater symptom severity [ 60 ].
There may be secondary effects of cannabinoids on HCV treatment side effects: However, there is also a potential drug-drug interaction between ribavirin, a traditional HCV treatment, and marijuana due to shared cytochrome metabolism [ 63 ]. Because 90 percent of HCV infections are the result of injection drug use [ 64 ], treatment of symptoms with marijuana may be contraindicated for this subpopulation, particularly because marijuana use in the context of other substance use i.
Given that newer treatments for HCV e. In sum, there is currently insufficient empirical support to recommend marijuana for the treatment of HCV. Marijuana use in HIV-infected patients is typically for the management of side effects e. Studies examining the effects of marijuana on the pharmacokinetics of antiretroviral medication demonstrated that neither smoked marijuana nor dronabinol affects short-term clinical outcomes e.
However, individuals who are dependent on marijuana have demonstrated poorer medication adherence and greater HIV symptoms and side effects than nonusers and nondependent users [ 69 ]. Furthermore, while some studies have no participant withdrawal due to adverse events [ 21 ],[ 70 ],[ 71 ], others reported treatment-limiting adverse events [ 26 ],[ 72 ],[ 73 ].
Finally, because drug use is a risk factor for HIV infection [ 74 ], treatment of symptoms with marijuana may be contraindicated for this subpopulation. Multiple sclerosis and muscle spasticity. Muscle spasticity, a common feature of MS, is disordered sensorimotor control that leads to involuntary muscle activation [ 75 ] that results in pain, sleep disturbance, and increased morbidity[ 76 ].
The majority of studies examining spasticity have compared oral or sublingual forms of cannabinoids to placebo and found reduced spasm severity [ 77 ]-[ 84 ], with symptom improvement enduring at long-term follow-up [ 85 ]-[ 87 ], and also reduced spasm frequency and spasm-related pain and sleep disturbances [ 77 ],[ 88 ],[ 89 ]. With regard to smoked marijuana, one study found reductions in muscle spasticity [ 90 ]; however, another study showed that smoking marijuana impaired posture and balance in individuals with spasticity [ 91 ], so there is currently insufficient evidence to determine the efficacy of smoked marijuana on spasticity [ 5 ].
Surveys of patient populations show that between 14 and 16 percent of patients with MS report using marijuana for symptom management [ 92 ],[ 93 ] and that compared to non-marijuana-using individuals with MS, marijuana-using individuals with MS have decreased cognitive functioning[ 90 ],[ 94 ],[ 95 ]. Because cognitive dysfunction is present in 40—60 percent of individuals with MS before marijuana administration [ 96 ], marijuana use may further compromise impaired cerebral functioning in a neurologically vulnerable population.
Additionally, future studies should carefully consider outcome assessment. The primary methods of measuring spasticity, the Ashworth Scale and patient self-report, may not be appropriate measures because antispastic drugs do not decrease Ashworth ratings, and patient-reported spasticity severity may be poorly correlated with patient functioning i.
Importantly for both MS and other neurological disorders, the American Academy of Neurology does not advocate the use of marijuana for the treatment of neurological disorders, due to insufficient evidence regarding treatment efficacy [ 98 ]. There has been a recent emergence of empirical studies of the effects of marijuana on symptoms of PTSD, borne primarily out of the observation that individuals with PTSD report using marijuana to cope with PTSD symptoms; specifically, hyperarousal, negative affect, and sleep disturbances[ 99 ]-[ ].
Empirical work has consistently demonstrated that the endocannabinoid system plays a significant role in the etiology of PTSD, with greater availability of cannabinoid type 1 receptors documented among those with PTSD than in trauma-exposed or healthy controls [ ],[ ]. Though the use of marijuana and oral THC [ ],[ ] have been implicated as a potential mechanism for the mitigation of many PTSD symptoms by way of their effects on the endocannabinoid system, some researchers caution that endocannabinoid activation with plant-based extracts over extended periods may lead to a number of deleterious consequences, including receptor downregulation and addiction [ ].
One unpublished pilot study of 29 Israeli combat veterans showed reductions in PTSD symptoms following the administration of smoked marijuana, with effects seen up to one year post-treatment[ ]. Remaining studies have been primarily observational in nature, documenting that PTSD is associated with greater odds of a cannabis use disorder diagnosis [ ] and greater marijuana craving and withdrawal immediately prior to a marijuana cessation attempt [ ]. Indeed, sleep difficulties a hallmark of PTSD have been associated with poor marijuana cessation outcomes[ ],[ ], while cannabis use disorders have been associated with poorer PTSD treatment outcomes [ ].
Severe and chronic pain. Clinical trials have examined smoked and oral administration of cannabinoids on different types of pain e. Two meta-analyses have been conducted examining the association between marijuana and pain. In the first, 18 RCTs demonstrated that any marijuana preparation containing THC, applied by any route of administration, significantly decreased pain scores from baseline compared to placebo [ ].
CBD does all this by stimulating the endocannabinoid system. Named after the plant that led to its discovery, the endocannabinoid system is a network of receptors located throughout the body. Short-lived natural endocannabinoid substances are synthesized on demand by the body to maintain homeostasis, a stable internal environment.
Research also suggests that supplementing can coax the body to build more receptors so natural cannabinoids will work more effectively. Two types of receptors have been identified: CB1 receptors, predominantly in the brain, nervous system, glands and organs; and CB2 receptors, found mainly in the regulatory cells of the immune system. Many tissues contain both receptors, each linked to a different action.
A key role of the endocannabinoid system is controlling inflammation by up-regulating or down-regulating the immune response. An overactive response can lead to allergies and auto-immune problems; an underactive one can leave the body susceptible to infections and the unchecked proliferation of cancer cells.
Although hemp and marijuana are both classified as cannabis, they are distinctly different varieties. It has no unpleasant side effects, and hemp products containing less than. CBD from hemp is not regulated as a drug, has no known toxic level, and it is impossible to overdose. CBD is available in many convenient forms. Dosage can vary quite a bit from one situation to the next. It may be necessary to experiment a little to find the right amount, and how often to give.
Typical suggested starting dose:
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