Researchers are calling for formal clinical trials into the efficacy of marijuana for treating opioid use disorder after a newly published study found that cannabis may ease many common symptoms of opioid withdrawal.
The study, conducted by researchers at the Johns Hopkins University School of Medicine and published in the forthcoming issue of the Journal of Substance Abuse Treatment, asked 200 people with past-month opioid and marijuana use whether their symptoms of opioid withdrawal improved or worsened when they consumed cannabis.
Of the 125 respondents who used marijuana to treat their withdrawal, nearly three-quarters (72 percent) said it eased their symptoms, while only 6.4 percent said it made them worse. Another 20 percent reported mixed results, and three people (2.4 percent) said cannabis didn’t seem to have an obvious effect either way.
“These results show that cannabis may improve opioid withdrawal symptoms and that the size of the effect is clinically meaningful.”
At least four states already include opioid use disorder (OUD) as a qualifying condition for medical marijuana, but critics have complained that there’s little evidence to support that policy. In the introduction to their new paper, the researchers acknowledge that “these approvals are concerning because of the limited and conflicting evidence suggesting cannabis can both improve and worsen opioid withdrawal and treatment retention.”
The results of their new study, however, suggest that cannabis is doing far more to ease opioid withdrawal symptoms than to make them worse. Of 18 common symptoms the researchers examined, participants on average said that cannabis helped ease every single one.
“Across all symptoms, more participants indicated that symptoms improved with cannabis compared to those that indicated symptoms worsened with cannabis,” the study found. “Ratios reflecting the participants who experienced improved versus worsened symptoms indicated that more individuals found cannabis to improve rather than worsen all evaluated symptoms.”
“Anxiety is the most common opioid withdrawal symptom improved with cannabis.”
The most frequently reported improved symptoms were anxiety (76.2 percent of respondents), tremors (54.1 percent), trouble sleeping (48.4 percent), bone and muscle aches (45.9 percent), restlessness (45.1 percent), nausea (38.5 percent) and opioid cravings (37.7 percent).
The most common symptoms reportedly made worse were yawning (7.4 percent), runny nose (6.6 percent), teary eyes (6.6 percent), restlessness (5.7 percent), vomiting (5.7 percent) and hot flashes (5.7 percent).
Women reported a significantly greater degree of symptom relief from marijuana than did men.
“On average, withdrawal severity scores nearly doubled on days cannabis was not used,” the study found. The results also inducted that people with “greater cannabis and opioid use experience greater reductions in opioid withdrawal when using cannabis.”
Participants were recruited using the Amazon Mechanical Turk (AMT) platform, a task-based crowdsourcing market.
“One limitation of this study,” the researchers acknowledged, “is that it was conducted using a crowdsourcing platform and, therefore, in-person validation of substance use was not possible.” Nevertheless, they noted that “studies have validated the use of AMT for substance use–related research by comparing MTurk data with data collected in in-person laboratory settings.”
Another limitation of the study is the subjectivity of the self-reported “Subjective Opiate Withdrawal Scale” (SOWS), which asks participants to evaluate the severity of their symptoms on a rubric, from 0 (not at all) to 4 (extremely severe).
“The SOWS has not been specifically evaluated for use as a retrospective measure,” the Johns Hopkins researchers wrote. “However, given the paucity of the data on this topic, the approach provided a feasible way to identify whether specific withdrawal symptoms may be differentially affected by cannabis use and the perceived magnitude of the effect of cannabis use on symptom severity.” Together, those variables “can be used to support prospective evaluation of this topic.”
The researchers don’t quite conclude that cannabis is beneficial for people going through opioid withdrawal, but they acknowledge that their data points to the need for further, more rigorous studies.
“These data suggest that the co-users of opioids and cannabis endorse cannabis as a method for reducing opioid withdrawal therapy,” the study says. “Given the shifting legal landscape, prospectively designed clinical trials that assess whether cannabis or its components can effectively treat opioid withdrawal are warranted.”
Though the matter is far from settled science, a number of other studies in recent years have suggested that cannabis may help reduce opioid use or dependency. Among them, a study published in December found that states with legal marijuana saw decreases in opioid prescriptions. A separate study from November of last year concluded that everyday cannabis use reduced opioid consumption among chronic pain patients.
The federal government is urging researchers to further investigate the role of cannabinoids in providing safer painkilling alternatives to opioids by making funding available for such studies.
Photo courtesy of Carlos Gracia.
Proof Of Marijuana Use Discovered At Ancient Biblical Site In Israel
An ancient biblical tribe in Israel likely used marijuana to produce hallucinogenic effects as part of cultic rituals, according to a new study that identified cannabis resin on an alter in a shrine built around 750 BCE.
Two alters that appeared near the entrance of the “Holy of Holies” in the Judahite shrine were excavated about 50 years ago and now an analysis of the materials on top of the alters turned up evidence of marijuana combustion at the site.
The study, published Thursday in the journal Tel Aviv, states that “cannabis inflorescences were burnt there, conceivably as part of a ritual that took place in the shrine.”
“It seems feasible to suggest that the use of cannabis on the Arad altar had a deliberate psychoactive role,” the study concluded.
“Cannabis odors are not appealing,” the researchers opined, “and do not justify bringing the inflorescences from afar. The frequent use of hallucinogenic materials for cultic purposes in the Ancient Near East and beyond is well known and goes back as early as prehistoric periods.”
However, this is the first time physical evidence has been identified that indicates the tribe of Judah participated in marijuana-infused ceremonies. Evidence of frankincense being burned was also found at the site.
The team behind the study, from the Israel Museum and the Volcani Center, relied on two common methods of identifying cannabinoids: liquid chromatography and gas chromatography. They found components of marijuana known widely today such as THC, CBD, CBN and various terpenoids.
Researchers said it’s unclear where the ancient tribe obtained cannabis, but they suspect that it “may have been imported from distant origins and were transported as dried resin (commonly known as hashish).”
To burn the marijuana and let out the smoke, it was apparently mixed with animal feces “to enable its mild heating,” the study states.
“It seems likely that cannabis was used at Arad as a deliberate psychoactive, to stimulate ecstasy as part of cultic ceremonies,” it continues. “If so, this is the first such evidence in the cult of Judah.”
“The discovery of cannabis on the smaller altar was a surprise. Arad provides the earliest evidence for the use of cannabis in the Ancient Near East. Hallucinogenic substances are known from various neighboring cultures, but this is the first known evidence of hallucinogenic substance found in the Kingdom of Judah.”
Eran Arie, a curator at the Israel Museum where the excavated shine is housed, told CNN that they “never thought about Judah taking part in these cultic practices.”
“The fact that we found cannabis in an official cult place of Judah says something new about the cult of Judah,” he said.
A separate study released last year documented how people from a diverse range of cultures have been using marijuana for thousands of years—in different forms and for different purposes. For example, cannabis was considered a “holy plant” in Tibet and was used in Tantric Buddhism to “facilitate meditations.” It was also used in Arabic medicine to treat ear infections, skin diseases, flatulence, intestinal worms, neurological pain, fever and vomiting.
Photo courtesy of Brian Shamblen.
THC-Infused Semen Can Be A Side Effect Of Frequent Marijuana Use, Study Finds
Many people have had to take a urine test for cannabis, perhaps as a job requirement. Using the popular procedure, marijuana metabolites can in some cases be detected for weeks after a person’s last use. But here’s a question few may have thought to ask: Can THC be detected in semen?
According to a new study by a team of Harvard Medical School researchers, the answer is yes—at least sometimes. In a study of 12 participants who regularly consumed marijuana by inhalation, the researchers were able to detect delta-9 THC, the main psychoactive ingredient in cannabis, in two subjects’ semen samples. And at least one metabolite of THC—what’s left over after the body processes the compound—could be detected in all samples capable of being analyzed. “Two semen samples,” the report says, “had insufficient volume to be analyzed.”
Why the focus on THC in semen? In a word, pregnancy. Men of reproductive age, the study’s authors note, “are the most prevalent consumers of marijuana, with 19.4% of men in the USA reporting use.” A 2018 study cited by the authors found that 16.5 percent of men and 11.5 percent of women reported using marijuana while attempting to conceive.
How exactly THC affects reproductive systems and childhood development are questions the Harvard authors don’t attempt to answer in the study. The primary goal of the proof-of-concept research, they explain, “was to determine whether THC can cross the blood-testis barrier.” On that front, they appear to have succeeded.
“In the setting of a growing repository of data surrounding the effects of the endocannabinoid system in the regulation and maintenance of fertility and early pregnancy,” the study says, “ours is the first report that the exogenous cannabinoid THC can be detected in any human reproductive matrix.”
Because of the interest in whether THC could be detected at all, researchers focused on regular, long-term marijuana consumers. All participants indicated they had used the drug between 25 and 30 days of the last month, and most said they had been regular consumers for at least five years. “Consequently,” the team said, “our study findings cannot be generalized to include ever users, light, or moderate users of marijuana.”
Of the two participants whose semen contained detectable levels of THC itself, samples contained 0.97 nanograms per milliliter and 0.87 ng/mL.
But it wasn’t clear what set those two participants apart. There was no correlation between semen THC and concentration of the metabolite THC carboxylic acid in urine, nor with time since last cannabis consumption, participant age or participant body mass index.
“It is puzzling that some, but not all, semen samples tested positive for THC,” the study says. “There were no obvious factors that were strongly associated with detectable semen THC; thus, we can propose few predictors of the presence of THC in human semen. Future directions (of research) include identifying characteristics that may affect semen detectable THC levels.”
How precisely THC affects semen—or the sperm within it, not to mention conception, pregnancy or childhood development—is still hard to say with certainty. As the Harvard researchers note in the study, “Evidence linking marijuana to reproductive outcomes is scarce and to date, often conflicting.”
One study of 1,200 young Danish men, for example, found that those who smoked marijuana regularly had lower sperm counts than those who did not. Another study, of 662 older, subfertile men in Massachusetts, found that men who had ever smoked marijuana had significantly higher sperm counts than those who’d abstained.
As for the effects of THC on sperm, or conception itself, those also remain unclear. “The effect of marijuana on human gametes and fertilization is relatively unknown,” the new paper says. Endocannabinoid receptors have been reported on sperm themselves, but “studies examining the direct effect of THC on human sperm are limited.”
Most research so far has either been observational, by measuring THC through self-reporting or blood testing, or studied the behavior of sperm that had been washed in a laboratory with a THC solution. “Our findings, that THC can be directly quantified in human seminal fluid, lay the groundwork to allow for future studies,” the new study says. “Since THC can be detected in the seminal fluid of some individuals, this might provide a direct method of measurement (rather than relying on self-reporting marijuana use, which is subjective and potentially unreliable, or serum levels which only reflect recent exposure) to bridge real-world clinical studies with the prior staged studies in which THC was directly incubated with washed sperm.”
While the THC-washed sperm showed some concerning effects, including decreased motility and mitochondrial oxygen consumption, the Harvard team acknowledged the concentrations of THC used in those studies were significantly stronger than anything observed in their semen study: “It should be noted that even the lowest concentration of THC with which former studies incubated sperm was over tenfold higher than the concentration of THC detected in the semen of our study subjects.”
In other words, the study is a stepping-stone to further research. And while the top-line findings might elicit some giggles, authors say the study is serious business.
“The ability to quantify cannabinoids in human reproductive tissues and fluids,” they conclude, “gives us the capability to directly study the effects of cannabis on early human reproduction.”
States With Medical Marijuana Laws Saw 20% Drop In Some Opioid Prescriptions
States with active medical marijuana laws saw certain opioid prescription rates drop nearly 20 percent compared to prohibition states, a first-of-its-kind study out of Columbia University’s Irving Medical Center has found. Authors said the findings underscore the importance of providing patients with pain management alternatives, such as cannabis, in efforts to reduce opioid use.
Drug overdoses remain a leading cause of injury-related death in the United States, and the U.S. Centers for Disease Control and Prevention reports that 68 percent of those deaths involve illicit or prescription opioids. The new study examines opioid prescriptions made specifically by orthopedic surgeons, who it notes are the nation’s third-highest prescribers of opioids.
“Although our study does not support a direct causal relationship, these population-level findings show that legalization of medical cannabis and patient access to dispensaries may be associated with reductions in opioid prescribing by orthopaedic surgeons,” the study’s authors concluded. “The observed trends reported in this study may be a reflection of growing availability of alternative pain management options for patients.”
“We found that overall opioid prescribing by orthopaedic surgeons in this cohort was reduced in states permitting patient access to medical cannabis, compared with those who do not.”
Analyzing nationwide Medicare Part D prescription drug data, researchers measured the aggregate daily doses of opioid medications prescribed by orthopedic surgeons in each state annually. They then looked for associations between that state-level data and the legal status of medical marijuana in each state.
As with past studies examining correlations between medical marijuana and opioid prescriptions, the Columbia analysis found a marked drop in prescriptions among states with medical cannabis laws (MCLs). “State MCLs were associated with a statistically significant reduction in aggregate opioid prescribing of 144,000 daily doses (19.7% reduction) annually,” the study, published this month in the Journal of the American Academy of Orthopaedic Surgeons, says.
Medical cannabis laws “were associated with a statistically significant reduction of 72,000 daily doses of hydrocodone annually.”
Not all state legal marijuana programs operate the same way, of course. It can also take years after a state adopts a medical cannabis law before its program is up and running. So the researchers looked at various specific factors, including when storefront dispensaries opened, whether state laws allowed home cultivation by patients, and whether recreational cannabis was legal for adults in each state.
Of the relationships that the researchers found were statistically significant, two stood out most clearly: States with active medical cannabis laws saw a 19.7 percent reductions in Medicare Part D opioid prescriptions made by orthopedic surgeons compared to states without medical cannabis laws. On a more granular level, states with operating storefront dispensaries saw a 13.1 percent reduction in those prescriptions.
Other relationships found by the researchers were just as likely to be due to chance. States with restrictive medical cannabis laws that allowed access only to low-THC products, for example, saw small, statistically insignificant increases in opioid prescriptions.
Researchers also “did not observe any significant association between total opioid prescriptions and home cultivation–only” medical cannabis laws, and concluded that “no significant association between recreational marijuana legalization and opioid prescribing was found.”
In “states that allow physicians to recommend medical cannabis to patients for any reason, there was a significant reduction in prescriptions for fentanyl…”
Cannabis is a particularly appealing alternative pain medication to study the effect of, the authors wrote, “because of its efficacy in treatment of chronic and acute pain and its potential for replacing and/or reducing opioid treatment.”
Researchers adjusted some of their data to better reflect not just the laws on the books but the actual accessibility of medical marijuana in each state. New York, for example, adopted a medical cannabis law in 2014, but home cultivation was prohibited and dispensaries didn’t open until 2016. “As such,” the authors wrote, “we did not classify New York as an MCL state or a dispensary-based MCL state until 2016.”
The study also cautions that its results only mean so much. Because it relied on population-level data and didn’t track individuals’ opioid or medical marijuana use, “we could not make any conclusions about any direct effect of substitution of opioids for cannabis by patients on prescription trends.” the authors wrote. “As such, our study does not draw conclusions of direct causation, but reports observed associations over time using a nationwide cohort database and multivariable regression analysis.”
Still, the study’s results contribute to a growing body of research indicating that medical cannabis accessibility significantly reduces statewide opioid use—and even opioid deaths. As the Columbia authors note in their report, “Multiple large nationwide database studies have shown that states with the legalization of medical marijuana have seen reductions in the opioid prescription rates and opioid-related mortality rates. The authors of these studies have theorized that in states where medical cannabis is more available, patients are likely to substitute cannabis for opioids in their pain management.”
For example, a meta-study that was recently published also signaled that marijuana shows promise as a treatment option for chronic pain and could serve as an alternative to opioid-based painkillers.
Last month, researchers released a study that found cannabis can mitigate symptoms of opioid withdrawal.
In December, researchers determined that states with legal marijuana access experience decreases in opioid prescriptions, and a separate study released the previous month showed that daily marijuana consumption is associated with reduced opioid consumption among chronic pain patients.