Cannabis Could Increase Men’s Sperm Count

Cannabis Could Increase Men's Sperm Count


Men who have smoked marijuana at some point in their life had significantly higher concentrations of sperm when compared with men who have never smoked marijuana, according to new research led by Harvard T.H. Chan School of Public Health. The study, conducted in the Fertility Clinic at Massachusetts General Hospital, also found that there was no significant difference in sperm concentrations between current and former marijuana smokers.

“These unexpected findings highlight how little we know about the reproductive health effects of marijuana, and in fact of the health effects of marijuana in general,” said Jorge Chavarro, associate professor of nutrition and epidemiology at Harvard Chan School. “Our results need to be interpreted with caution and they highlight the need to further study the health effects of marijuana use.”

The study will be published on February 5, 2019 in Human Reproduction.

It is estimated that 16.5 percent of adults in the US use marijuana, and support for legal recreational use of marijuana has increased dramatically in recent years. Understanding the health effects associated with marijuana use is important given the growing perception that it poses few health hazards.

The researchers hypothesized that marijuana smoking would be associated with worse semen quality. Previous studies on marijuana have suggested that it is associated with negative effects on male reproductive health, but most of those studies had focused on animal models or on men with histories of drug abuse.

For this study, researchers collected 1,143 semen samples from 662 men between 2000 and 2017. On average, the men were 36 years old, and most were white and college educated. Additionally, 317 of the participants provided blood samples that were analyzed for reproductive hormones. To gather information on marijuana use among study participants, researchers used a self-reported questionnaire that asked the men a number of questions about their usage, including if they had ever smoked more than two joints or the equivalent amount of marijuana in their life and if they were current marijuana smokers.

Among the participants, 365, or 55 percent, reported having smoked marijuana at some point. Of those, 44 percent said they were past marijuana smokers and 11 percent classified themselves as current smokers.

Analysis of the semen samples showed that men who had smoked marijuana had average sperm concentrations of 62.7 million sperm per milliliter of ejaculate while men who had never smoked marijuana had average concentrations of 45.4 million sperm per milliliter of ejaculate. Only 5 percent of marijuana smokers had sperm concentrations below 15 million/mL (the World Health Organization’s threshold for “normal” levels) compared with 12 percent of men who had never smoked marijuana.

The study also found that among marijuana smokers, greater use was associated with higher serum testosterone levels.

The researchers cautioned that there are several potential limitations to the findings, including that participants may have underreported marijuana use given its status as an illegal drug for most of the study period. The researchers emphasized that they do not know to what extent these findings may apply to men in the general population as the study population consisted of subfertile men in couples seeking treatment at a fertility center. Additionally, they noted that there are few similar studies to compare their results against.

“Our findings were contrary to what we initially hypothesized. However, they are consistent with two different interpretations, the first being that low levels of marijuana use could benefit sperm production because of its effect on the endocannabinoid system, which is known to play a role in fertility, but those benefits are lost with higher levels of marijuana consumption,” said Feiby Nassan, lead author of the study and a postdoctoral research fellow at Harvard Chan School. “An equally plausible interpretation is that our findings could reflect the fact that men with higher testosterone levels are more likely to engage in risk-seeking behaviors, including smoking marijuana.”

Medical Cannabis for IBD: Is the Web Reliable?

The quality of information on the web about medical marijuana for inflammatory bowel disease (IBD) was only “average,” a researcher reported here.

On the validated DISCERN questionnaire used to assess quality of information, the average score was 42.6, which was classified as average, according to Marie Borum, MD, and colleagues from George Washington University in Washington.

IBD is one of the conditions for which medical marijuana has been approved as a treatment. “Based on observational and animal studies, it is thought that modulation of endocannabinoid receptors may improve inflammation and therefore the symptoms of IBD,” Borum’s group explained in a poster at the Advances in Inflammatory Bowel Diseases annual meeting.

Patients increasingly use the internet to find information about alternative treatments, and no studies have evaluated online resources about medical marijuana for IBD. This study aimed to evaluate claims, warnings, and evidence on the available internet resources for IBD.

On the DISCERN quality questionnaire, scores of 66 to 75 were considered excellent, 56 to 65 were very good, 46 to 55 were good, 36 to 45 were average, and <35 were poor.

A total of 89 web sites were included, of which 75 (84%) were intended for use by consumers and 14 (16%) were aimed at medical professionals.

The average Flesch-Kincaid grade of readability was 13.3, with no significant difference between sites intended for consumers (13.2) and for medical professionals (14, P=0.41). This test estimates the grade level for readability, and reflects the average sentence length and the average number of syllables per word. For example, a Flesch-Kincaid grade of 10.6 represents an 11th grade reading level, while a grade of 14 represents the second year of college.

On the discernment quality score, there was no difference between the consumer and medical professional web sites (40 vs 48, P=0.08).

Consumer web sites did, however, offer significantly more claims of improvement in disease pathology than did sites for professionals (45% vs 15%, P=0.04) and significantly less often provided evidence-based references (40% vs 85%, P=0.04).

Only 21.3% of the sites included precautionary information regarding marijuana use in IBD, with no significant difference seen between sites aimed at consumers and those intended for medical professionals.

The study demonstrated that a multitude of online resources exist with information of medical marijuana as an alternative treatment for IBD patients.

The majority of sites were intended for consumers, but their readability grade level exceeded the NIH recommendation of a sixth grade reading level for medical information, the researchers pointed out.

There also was variability in the available evidence-based references, and inconsistency in the inclusion of precautionary information and therapeutic claims.

“It is critical that readily available online information about cannabis treatment in IBD be readable, evidence-based, and comprehensive in order to allow patients to make informed medical decisions,” they concluded.

Benefits of Medical Cannabis for Resistant Epilepsy Time-Limited?

Patients with treatment-resistant epilepsy can develop a tolerance to cannabis-based therapy, a finding that may have implications for long-term management, new research suggests.

Dr Shimrit Uliel-Sibony


“Physicians should be aware that tolerance may occur,” study investigator Shimrit Uliel-Sibony, MD, pediatric epileptologist, Dana-Dwek Children’s Hospital, Tel Aviv University, Israel, told Medscape Medical News.

“There’s this notion that cannabis is a great medicine, that it’s much better in terms of response rates than other interventions for patients with treatment-resistant epilepsy, but that may only be at the beginning,” she added.

Long-term exposure may produce a different picture. With time, efficacy may decrease, resulting in a need to increase the dose. This suggests the development of tolerance.

“We know marijuana may have cognitive consequences with long-term, chronic recreational use. I think we need to be a little more cautious on our expectations of this therapy,” said Uliel-Sibony.

The study was presented here at the American Epilepsy Society (AES) 72nd Annual Meeting 2018.

Few Long-term Data

In the recent past, many studies have suggested that medical cannabis is superior to traditional antiepileptic drugs (AEDs). Studies have reported dramatic improvement in seizure control, as well as a favorable safety profile.

However, said Uliel-Sibony, there is a need for data on long-term safety and efficacy. The long duration of treatment, the investigators note, “raises the possibility of withdrawal and tolerance.” Some animal studies suggest that prolonged exposure to tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis, but not cannabidiol (CBD) leads to tolerance.

To assess the long-term efficacy of cannabinoids as well as the development of tolerance in the treatment of refractory epilepsy, the investigators conducted an observational, longitudinal study of pediatric and adult patients.

The analysis included 92 patients (59 males) ranging in age from 1 year to 37 years (mean age, 11.8 years). All had treatment-resistant epilepsy; two had Dravet syndrome; and three had Lennox-Gastaut syndrome (LGS). The remainder had other types of seizures and epilepsy syndromes.

All patients had experienced treatment failure with numerous drug therapies, and for some, use of the ketogenic diet or vagal nerve stimulation therapy was also ineffective. None had been previously treated with medical cannabis.

Participants were initially given a cannabis oil extract in which the ratio of CBD to THC was 20:1. That amount of THC has negligible psychoactive activity, noted Uliel-Sibony.

The patients had been receiving stable doses of AEDs for at least 4 weeks before study enrollment. All participants had at least 3 months of follow-up (mean follow-up, 20 months).

No “Honeymoon” Tolerance

Tolerance was defined as a 30% or greater reduction in response rate that continued for more than 3 months.

Patients in whom efficacy decreased during the first 3 months of treatments were not included. The intention was to exclude patients who showed short-lasting improvement that was possibly the result of the “honeymoon” effect.

The investigators found that about 29% of the study population experienced a reduction in seizures by 50% to 75%.

Of 84 patients included in the tolerance analysis, 25% developed tolerance, which was reported with an average dosage of 12.6 mg/kg/day.

This dosage is lower than in some studies that used more purified cannabis. There was some suggestion that combining CBD with a very small amount of TCH “enables use of a lower dose of CBD,” a phenomenon referred to as the entourage effect, said Uliel-Sibony.

None of the patients with Dravet syndrome or LGS developed tolerance, she added.

In an attempt to counteract tolerance, the CBD dose was increased. Using this approach, about 20% of the patients were able to achieve the same response rate as before the development of tolerance, but this was not the case for almost half of the cohort.

In some patients, tolerance was reversed by gradually reducing the CBD dose, waiting 2 to 3 weeks, and then restarting the medication at the same dose that achieved response.

The tolerance may be due to “receptor desensitization,” said Uliel-Sibony. “If we take patients off the medicine, the receptors become sensitive again.”

This new study used two similar CBD products that are available in Israel. There was no difference between the two products in terms of tolerance.

It is not clear whether the tolerance seen in the study was due to the presence of THC. The literature on the subject suggests that there is no tolerance to CBD, only to THC, she said.

But it may be a question of exposure. In this study, the mean time for tolerance to occur was 7.3 months.

“Tolerance is something that develops over time,” said Uliel-Sibony.

Having a small amount of THC in the product seems to have some positive side effects, she said. Parents reported that children showed improvements in sleep and appetite and that they were more alert.

Great Expectations

She noted that overall, the side effect profile for the formulation is superior to that reported in other studies that used a more purified formulation of CBD. Of the 87 patients included in the safety analysis, 51% experienced adverse reactions.

Uliel-Sibony hopes to continue to follow the patients in the study for a longer period “to get a better picture” of tolerance, she said.

But she recognizes the challenges of following this patient population. Moreover, even if the number of seizures is reduced by half, for those patients who were having 10 seizures at the start of treatment, the condition is still not well controlled.

She believes expectations are high for cannabis-based therapy. She cited one study that showed that parents who relocated to Colorado just to access one of the early CBD treatments for epilepsy reported better response to the drug.

Families may be misled by some of the hype surrounding medical marijuana, said Uliel-Sibony. “Parents believe they’re giving their child something natural, something that isn’t really a chemical, but CBD is a medicine like any other.”

She noted that her study has limitations, including the fact that it is not randomized controlled trial.

How Cannabis Can End the Use of Dangerous Prescription Pain Killers

Opioid painkiller prescriptions have jumped 300 percent in the last decade, and they are now the most commonly prescribed drugs on the market. They are also the most dangerous and addictive drugs on the market, and often lose effectiveness with long-term use.

Now a new study conducted by researchers at The University of New Mexico, involving medical cannabis and prescription opioid use among chronic pain patients, found a distinct connection between having the ability to use cannabis and significant reductions in opioid use.

There is an abundance of evidence that the suppression of medical marijuana is one of the greatest failures of a free society, journalistic and scientific integrity as well as our fundamental values. There is no plant on Earth more condemned than cannabis, yet it has the potential to heal dozens of diseases and curb our rampant use of prescription opioids. Some studies have suggested that marijuana may even have a place in curbing the opioid epidemic.

The study, titled “Associations between Medical Cannabis and Prescription Opioid Use in Chronic Pain Patients: A Preliminary Cohort Study” and published in the open access journal PLOS ONE, was conducted by Dr. Jacob Miguel Vigil, associate professor, Department of Psychology and Dr. Sarah See Stith, assistant professor, Department of Economics. The results from this preliminary study showed a strong correlation between enrollment in the New Mexico Medical Cannabis Program (MCP) and cessation or reduction of opioid use, and that whole, natural Cannabis sativa and extracts made from the plant may serve as an alternative to opioid-based medications for treating chronic pain.

Today, opioid-related drug overdoses are the leading cause of preventable deaths in the United States killing approximately 100 Americans every day. Conventional pharmaceutical medications for treating opioid addiction, such as methadone and buprenorphine, can be similarly dangerous due to substantial risks of lethal drug interactions and overdose.

“Current levels and dangers of opioid use in the U.S. warrant the investigation of harm-reducing treatment alternatives,” said Vigil, who led the study. “Our results highlight the necessity of more extensive research into the possible uses of cannabis as a substitute for opioid painkillers, especially in the form of placebo-based, randomized controlled trials and larger sample observational studies.”

Cannabis has been investigated as a potential treatment for a wide range of medical conditions from post-traumatic stress disorder to cancer, with the most consistent support for the treatment of chronic pain, epilepsy and spasticity. In the U.S., states, including New Mexico, have enacted MCPs in part for people with chronic, debilitating pain who cannot be adequately or safely treated with conventional pharmaceutical medications.

In a historic and significant moment in American history, in November of 2012, Colorado became the first US state to legalize cannabis for recreational use. The impact of the decision has rippled across the entire country with vast opportunities to educate millions on the top health benefits of cannabis and specifically for pain.

Like other states, New Mexico only permits medical cannabis use for patients with certain debilitating medical conditions. All the patients in the study had a diagnosis of “severe chronic pain,” annually validated by two independent physicians, including a board-certified specialist.

New Mexico, Dr. Vigil notes, is among the U.S. states hardest hit by the current opioid epidemic, although the number of opioid-related overdose deaths appears to have fallen in recent years, perhaps the result of increased enrollment in the NM MCP, which currently includes more than 48,000 patients.

“MCPs are unique, not only because they allow patients to self-manage their cannabis treatment, but because they operate in conflict with U.S. federal law, making it challenging for researchers to utilize conventional research designs to measure their efficacy,” Vigil said.

The purpose of the researchers’ preliminary, cohort study was to help examine the association between enrollment in a MCP and opioid prescription use. The study observed 37 habitual opioid using, chronic pain patients that chose to enroll in the MCP between 2010 and 2015, compared to 29 patients with similar health conditions that were also given the option, but ultimately chose not to enroll in the MCP.

“Using informal surveys of patients enrolled in the MCP, we discovered a significant proportion of chronic pain patients reporting to have substituted their opioid prescriptions with cannabis for treating their chronic pain,” said Vigil.

The researchers used Prescription Monitoring Program opioid records over a 21-month observation period (first three months prior to enrollment for the MCP patients) to more objectively measure opioid cessation — defined as the absence of opioid prescriptions activity during the last three months of observation, with use calculated in average daily intravenous [IV] morphine dosages. MCP patient-reported benefits and side effects of using cannabis one year after enrollment were also collected.

By the end of the observation period, the data showed MCP enrollment was associated with a 17 times higher age- and gender-adjusted odds of ceasing opioid prescriptions, a 5 times higher odds of reducing daily prescription opioid dosages, and a 47 percentage point reduction in daily opioid dosages relative to a mean change of positive 10 percentage points in the non-enrolled patient group.

Survey responses indicated improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few negative side effects from using cannabis one year after enrollment in the MCP.

The researchers’ findings, which provide clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrant further investigations on cannabis as a potential alternative to prescription opioids for treating chronic pain.

According to Stith, “The economic impact of cannabis treatment should also be considered given the current burden of opioid prescriptions on healthcare systems, which have been forced to implement costly modifications to general patient care practices, including prescription monitoring programs, drug screening, more frequent doctor-patient interactions, treatment of drug abuse and dependence, and legal products and services associated with limiting opioid-related liability.”

“If cannabis can serve as an alternative to prescription opioids for at least some patients, legislators and the medical community may want to consider medical cannabis programs as a potential tool for combating the current opioid epidemic,” Vigil said.

“All Cannabis Use is Medicinal” Whether You Know it Or Not


In the past two years, we have witnessed a sea of change in the attitude of Americans toward cannabis. Colorado made history by becoming the first state to completely decriminalize possession and use of the plant, with Washington and other states soon following.

Medical cannabis use is now legal in 23 states, and others will soon be joining that list. Polls find that a solid majority of Americans support cannabis legalization, especially for medicinal use. The Free Thought Project has reported on many incredible ways that cannabis is being used to treat a variety of ailments. Its effectiveness at reducing or eliminating epileptic seizures is nothing short of amazing.

 People are also realizing that the war on cannabis—and all drugs for that matter—is a war on people carried out by law enforcement to restrict freedom and to extort millions of dollars for victimless behavior. The Drug Enforcement Agency (DEA) gains a sizable amount of revenue through cannabis seizures. The dried plant also provides ample opportunity for local law enforcement to carry out its favorite, most insidious form of extortion known as Civil Asset Forfeiture.

The good news is that these abuses of human rights are being exposed, and law enforcement is sounding ever more desperate as justification for their actions withers under the advance of reason and logic. When cannabis is finally decriminalized everywhere, our evolution from the days of Reefer Madness will provide an entertaining yet tragic documentary.

The fight continues, and we must build on the momentum if we are to see it to completion. The arguments for legalization are many, and they are sound. But perhaps the entire narrative needs to be reconsidered as we make the final push.


Cannabis goes on sale in Colorado

David Martinez, manager of 3D Cannabis Center in Denver, on 31 December 2013
Shops selling cannabis have been preparing for a huge influx of customers on their first day of trading

The US state of Colorado is making history by becoming the first to allow stores to sell cannabis.

As many as 30 stores around the state are expected to start selling the drug for recreational purposes from 1 January, dubbed Green Wednesday.

Colorado, along with Washington state, voted to legalise the use and possession of cannabis for people over the age of 21 in November 2012.

Washington is not expected to allow the sale of it until later in 2014.

Colorado and Washington are among 20 states to have approved marijuana use for medical purposes. The drug is still illegal under federal law.

‘Who knows?’

Store owners had stocked up, prepared celebrations and hired extra security in preparation for their opening on Green Wednesday.

“Start Quote

It’s almost the worst of both worlds”

Kevin Sabet Smart Approaches to Marijuana

Under the new law, cannabis will be sold like alcohol. Residents will be able to buy up to one ounce, while those from out of the state can purchase up to a quarter of an ounce.

Cannabis can only be smoked on private premises, with the permission of the owners.

The sale of the drug will be taxed in the same way as alcohol, and state officials have said they expected it to raise millions – the first $40m of which will be used for school construction, The Denver Post reports.

It was not clear exactly how many shops were expected to open on New Year’s Day, though around 30 were listed by The Denver Post.

A total of 136 stores have been given licenses to sell marijuana. Most of the shops are based in Denver. Some communities elsewhere in Colorado have exercised their right not to have the stores.

Supporters of legalising cannabis have praised Colorado’s move.

Rachel Gillette, of the Colorado branch of the National Organization for the Reform of Marijuana Laws, said the state “has found an exit strategy for the failed drug war and I hope other states will follow our lead”.

But critics say it sends the wrong message to the nation’s youth and fear it will lead to serious public health and social problems.

“There will still need to be a black market to serve people who are ineligible to buy on a legal market, especially kids,” said Kevin Sabet of Smart Approaches to Marijuana. “It’s almost the worst of both worlds.”

Medical marijuana to be available in Canada on open market.

Ailing Canadians were only hours away from being able to legally buy marijuana for medical purposes on the free market, officials said Monday.

As of Tuesday, Health Canada will phase out a system of homegrown marijuana for a factory-style operation that will grow, package and distribute a variety of marijuana, the Toronto Star reported Sunday.

 About 37,400 patients use medical marijuana, Health Canada says. That number is expected to rise to as many as 450,000 by 2024.

The sanctioned growers are required to raise the plants indoors and have vaults and security systems to prevent thefts of their products, which could be sold on the black market. One firm plans to initially produce 20 strains.

Recreational use of marijuana will still be banned.

Since June, 156 companies have applied for licenses. The first two were awarded last week.

Under the system being phased out, about 4,200 people were licensed to grow marijuana on their property for no more than two patients each. That type of cottage industry will now be banned. The Royal Canadian Mounted Police has charged such operations were fronts for illegal activity.

The price of legal weed is expected to soon undercut the stuff sold on the streets, where it goes for about $10 a gram, or about $280 an ounce. Health Canada projects the factory-grown marijuana will retail next year for about $7.60 a gram, or $215 an ounce. Within 10 years, industry revenues are projected to reach $1.3 billion a year.

Sophie Galarneau, a senior Health Canada official, said she expects competition to eventually get the price down to $3 a gram, or about $85 an ounce.



Marijuana Cuts Lung Cancer Tumor Growth In Half, Study Shows.

The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.

They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.

THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.

“The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer,” said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. “When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays,” Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. “THC offers some promise, but we have a long way to go before we know what its potential is,” she said.


Seizure Disorders Enter Medical Marijuana Debate.

The role of cannabinoids in the treatment of seizure disorders in children has come under the spotlight in recent months amid a string of media reports of parents obtaining the substances in states where medical marijuana is now legal and claiming “miraculous” reductions in seizures with the treatment.

Among the reports was that of a 6-year-old boy with Dravet’s syndrome, a rare form of childhood epilepsy, reported by CNN. In an interview, the parents said the boy was left immobilized by the 22 antiseizure pills a day required to control his seizures, but after treatment with a liquid, nonpsychoactive form of marijuana, he was able to make it through an entire day without a seizure for the first time since he was 4 months old, and continued to see substantial reduction.

“Instead of medical marijuana, this is miracle marijuana,” the father told CNN.

Another child with Dravet’s syndrome in Colorado, who was having 300 grand mal seizures a week and had lost the ability to walk, talk, and eat, was similarly reported to have her seizures drastically reduced to just 3 times per month after treatment with the liquidized form of cannabis, CNN reported.

In both cases, the treatment was low in tetrahydrocannabinol, or THC, the compound associated with the psychoactive properties of marijuana, and high in cannabidiol, which is not psychoactive and is instead believed to be medicinal. Both cases were also featured in a CNN documentary on medical marijuana, “Weed,” that aired Sunday, August 11.

With the increasingly abundant anecdotal but very high profile reports, neurologists can likely expect a surge in interest from parents, particularly those frustrated by intractable epilepsy in their children, who are logically asking “why not?”

“When patients, children or otherwise, are faced with bad situations and no good treatment they, or their parents, look ‘out of the box’ to find one,” said David M. Labiner, MD, a neurologist with the University of Arizona and director of the Arizona Comprehensive Epilepsy Program, in Tucson.

“Medical marijuana is one of those things being utilized now,” he told Medscape Medical News.

He added, however, that despite the anecdotal reports, the bigger picture in terms of clinical evidence of efficacy, or, importantly, long-term safety on such treatments is lackluster at best. “There is limited high-quality evidence about the efficacy and virtually no data about the safety of using marijuana or cannabinoids,” he said.

Medical marijuana is currently legal in 18 states and the District of Columbia, and in some states the approval explicitly includes treatment for epilepsy.

But a 2012 Cochrane review of all published randomized controlled trials involving the treatment of marijuana or one of marijuana’s constituents in people with epilepsy concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy.”

With a primary outcome investigated for the trials of seizure freedom for 1 year or more or 3 times the longest interseizure interval, the researchers found 4 reports with a total of 48 patients randomly assigned to placebo or to 200 to 300 mg of cannabidiol per day.

Although none of the patients in the treatment groups were reported to have sustained adverse effects, none of the trials included reliable details of randomization and all were deemed to be of “low quality.”

In a commentary on the review, Jonathan W. Miller, MD, PhD, noted that in addition to the inconclusive evidence of efficacy, other evidence has suggested marijuana and low-dose THC can represent a possible seizure precipitant.

“Marijuana itself has major shortcomings as an epilepsy treatment,” writes Dr. Miller, who is director of Functional and Restorative Neurosurgery and director of Epilepsy Surgery at University Hospitals, Case Medical Center/Case Western Reserve University in Cleveland, Ohio. “Its psychotropic action can only be regarded as an adverse effect.”

“It is a biological product containing multiple compounds with unclear, possible, anti- or pro-convulsant effects, delivered in varying amounts from dose to dose,” he adds. “Long-term safety has not been adequately investigated.”

With the need for new epilepsy treatments pressing, however, he underscores the importance of evaluating the potential benefits of cannabinoids with more reliable clinical trials.

“Cannabidiol or other individual cannabinoids with minimal adverse effects could be extracted and given in precise doses in rigorously designed, blinded, randomized clinical trials to test efficacy and safety,” Dr. Miller urges. “This is a reasonable route for development of new antiepileptic drugs.”

Safe Dispensing a Concern

In the case of the California boy described in the CNN story, the parents said they obtained the cannabis from the Harborside Health Clinic, a medical marijuana dispensary in Oakland, California, that has billed itself as the “world’s largest pot shop” and sells concentrations with names such as “Deadhead OG” and “Afghani Hash.”

The clinic does claim to screen all of its products for safety and tests for potency as well as the presence of pathogenic molds, but Dr. Labiner, in agreement with Dr. Miller, asserted that if cannabinoids are shown to be effective anticonvulsants, they should be provided to the public with the same safety assurances as any other epilepsy drug.

“Rather than thinking about how to keep sick people from using these compounds, as many of our elected officials and law enforcement are doing, we need to support efforts to determine how to appropriately use these compounds in a controlled fashion and not delegate that responsibility to [places like] ‘the world’s largest pot shop’.”

Even the American Academy of Pediatrics (AAP) favors the pursuit of a better understanding of the potential benefits of medical marijuana, but, with the same concerns of operating in an unregulated environment in mind, the academy opposes laws legalizing medical marijuana.

“The AAP strongly supports more cannabinoid research to better understand both how these substances can be used therapeutically as well as their potential side effects — which we may well be underestimating,” said Sharon Levy, MD, MPH, director of the Adolescent Substance Abuse Program at Children’s Hospital Boston and an assistant professor of pediatrics at Harvard Medical School in Massachusetts.

“[But] the AAP does not support ‘medical marijuana’ laws as they circumvent regulations put in place to protect patients, and children are a particularly vulnerable population,” Dr. Levy told Medscape Medical News.

While noting that the reports on children finding seizure control from cannabinoids are “quite compelling,” Dr. Levy emphasized that medical marijuana as a policy misleads the public on the level of research behind the endorsement.

“It implies, incorrectly, that marijuana is an established medication and opens the doors to people and parents ‘experimenting’ with it for all kinds of conditions.”

And when it comes to experimenting with drugs to be used particularly on children, the practice is best left to experts in highly controlled conditions, she added.

“I fully support the parents who are trying to advocate for something they believe will be helpful for their children. But let’s do it the right way — the same way we develop all other medications. We are bound to make mistakes when we try and take short cuts.”




Medicinal Use of Marijuana — Polling Results.

Readers recently joined in a lively debate about the use of medicinal marijuana. In Clinical Decisions,1 an interactive feature in which experts discuss a controversial topic and readers vote and post comments, we presented the case of Marilyn, a 68-year-old woman with metastatic breast cancer. We asked whether she should be prescribed marijuana to help alleviate her symptoms. To frame this issue, we invited experts to present opposing viewpoints about the medicinal use of marijuana. J. Michael Bostwick, M.D., a professor of psychiatry at Mayo Clinic, proposed the use of marijuana “only when conservative options have failed for fully informed patients treated in ongoing therapeutic relationships.” Gary M. Reisfield, M.D., from the University of Florida, certified in anesthesiology and pain medicine, and Robert L. DuPont, M.D., a clinical professor of psychiatry at Georgetown Medical School, provide a counterpoint, concluding that “there is little scientific basis” for physicians to endorse smoked marijuana as a medical therapy.

We were surprised by the outcome of polling and comments, with 76% of all votes in favor of the use of marijuana for medicinal purposes — even though marijuana use is illegal in most countries. A total of 1446 votes were cast from 72 countries and 56 states and provinces in North America, and 118 comments were posted. However, despite the global participation, the vast majority of votes (1063) came from the United States, Canada, and Mexico. Given that North America represents only a minority of the general online readership of the Journal, this skew in voting suggests that the subject of this particular Clinical Decisions stirs more passion among readers from North America than among those residing elsewhere. Analysis of voting across all regions of North America showed that 76% of voters supported medicinal marijuana. Each state and province with at least 10 participants casting votes had more than 50% support for medicinal marijuana except Utah. In Utah, only 1% of 76 voters supported medicinal marijuana. Pennsylvania represented the opposite extreme, with 96% of 107 votes in support of medicinal marijuana.

Outside North America, we received the greatest participation from countries in Latin America and Europe, and overall results were similar to those of North America, with 78% of voters supporting the use of medicinal marijuana. All countries with 10 or more voters worldwide were at or above 50% in favor. There were only 43 votes from Asia and 7 votes from Africa, suggesting that in those continents, this topic does not resonate as much as other issues.

Where does this strong support for medicinal marijuana come from? Your comments show that individual perspectives were as polarized as the experts’ opinions. Physicians in favor of medicinal marijuana often focused on our responsibility as caregivers to alleviate suffering. Many pointed out the known dangers of prescription narcotics, supported patient choice, or described personal experience with patients who benefited from the use of marijuana. Those who opposed the use of medicinal marijuana targeted the lack of evidence, the lack of provenance, inconsistency of dosage, and concern about side effects, including psychosis. Common in this debate was the question of whether marijuana even belongs within the purview of physicians or whether the substance should be legalized and patients allowed to decide for themselves whether to make use of it.

In sum, the majority of clinicians would recommend the use of medicinal marijuana in certain circumstances. Large numbers of voices from all camps called for more research to move the discussion toward a stronger basis of evidence.


Medicinal use of marijuana. N Engl J Med 2013;368:866-868


Source: NEJM