The therapeutic application of cannabis has become increasingly prevalent across developed nations, yet the scientific evidence supporting its medical use remains surprisingly limited. A recent JAMA Clinical Reviews podcast featuring Dr Kevin Hill from Harvard Medical School reveals critical information that healthcare professionals and patients need to understand about the therapeutic use of cannabis and its associated risks.

According to recent data, approximately 27% of adults in the United States and Canada have used cannabis for medical purposes, whilst just over 10% have tried cannabidiol (CBD) for therapeutic reasons. This widespread adoption has occurred despite minimal regulatory approval and mounting evidence of significant health risks.

Understanding Cannabis and Its Components

Cannabis is a complex plant containing hundreds of chemical compounds, including flavonoids, terpenes, and cannabinoids. Whilst over 140 cannabinoids exist within the plant, medical discussions typically focus on two: delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive compound responsible for the “high” associated with cannabis use and can also trigger psychotic episodes. CBD, conversely, is not intoxicating, though it does affect how users feel.

The complexity of the therapeutic use of cannabis stems partly from its numerous formulations. People can smoke cannabis flower, consume edible products, vaporise the substance, or apply topical ointments. Each formulation delivers different potencies and onsets of action, with THC content being the critical variable across all forms.

Limited FDA Approvals for Therapeutic Use of Cannabis

Currently, only three cannabinoid medications have received approval from the US Food and Drug Administration. Dronabinol (pure THC) and nabilone (a CB1 receptor agonist) are approved for treating nausea and vomiting associated with cancer chemotherapy, as well as appetite stimulation in conditions like HIV. In 2018, one particular CBD formulation gained approval for treating two paediatric epilepsy conditions (Lennox-Gastaut and Dravet syndrome) and seizures associated with tuberous sclerosis in adults.

These limited approvals stand in stark contrast to the numerous conditions for which people currently use cannabis, often without solid scientific evidence supporting its efficacy.

Rising Potency and Escalating Risks

One of the most concerning trends in medicinal cannabis use involves dramatically increasing potency levels. During the 1960s, 1970s, and 1980s, typical cannabis contained three to four percent THC. Published research from the University of Mississippi now shows typical potency hovering near 20 percent THC. This fivefold increase has profound implications for both acute and chronic health effects.

Acute risks associated with cannabis use include impaired judgement, motor skill deficits, elevated heart rate, and transient psychosis. These immediate effects can compromise driving ability and decision-making, posing risks not only to users but to those around them.

Chronic Health Effects and Medicinal Cannabis

The chronic effects of cannabis prove particularly problematic for individuals using daily or near-daily. Dr Hill emphasised that most adverse effects relate to THC rather than CBD, though CBD can cause problems as well. Brain-related complications include addiction, cannabis hyperemesis syndrome (severe cyclical vomiting), and worsening of various psychiatric conditions.

Recent epidemiological research published in JAMA Psychiatry revealed a striking statistic: 34.8% of adult cannabis users develop cannabis use disorder. This represents a significant increase from previous estimates of 10 to 30 percent. For those using cannabis for medical purposes specifically, approximately 29% develop use disorder.

Physical health impacts have become increasingly well-defined through research. Cardiovascular adverse effects, pulmonary complications, and chronic neurocognitive deficits all occur with regular cannabis use. These risks accumulate over time, particularly amongst daily users.

Therapeutic Use of Cannabis and Addiction Risk

Cannabis use disorder represents a significant concern that clinicians must monitor carefully. Warning signs include tolerance (requiring increasingly larger amounts to achieve the same effect), withdrawal symptoms upon cessation, and spending excessive time obtaining or using cannabis at the expense of work, school, or relationship responsibilities.

Diagnostic criteria specify that experiencing two or more of eleven specific factors within a 12-month period indicates cannabis use disorder. Healthcare professionals working with patients considering the therapeutic use of cannabis must remain vigilant for these signs, as addiction can develop even when use begins for legitimate medical reasons.

Particular Concerns for Young People

The developing brain faces unique vulnerabilities to cannabis exposure. Human brains continue developing into the mid-20s, and research demonstrates that early and regular cannabis use can significantly impair cognitive abilities. A 2012 study published in the Proceedings of the National Academy of Sciences found that young people using cannabis daily or near-daily experienced up to an eight-point decline in IQ over time. This represents more than one standard deviation, a statistically and clinically significant reduction.

These findings underscore the importance of preventing cannabis use amongst adolescents and young adults, whose neural development remains incomplete and particularly susceptible to disruption.

The Evidence Gap in Medicinal Cannabis Use

A critical issue confronting healthcare professionals involves patients using cannabis for conditions lacking solid scientific support. Whilst people suffering from chronic medical conditions naturally seek relief, the evidence base for the therapeutic use of cannabis remains limited primarily to the FDA-approved conditions mentioned earlier.

Dr Hill emphasised the importance of clinicians engaging in evidence-based conversations with patients. When patients express determination to use cannabis despite limited evidence, healthcare professionals face the challenging task of providing informed guidance whilst acknowledging the significant risks involved.

Concerns About Concurrent Substance Use

Cannabis use becomes particularly dangerous when combined with alcohol or benzodiazepines. These combinations amplify impairment and increase risks of accidents, respiratory depression, and poor decision-making. Healthcare professionals must clearly communicate these dangers to any patients considering medicinal cannabis.

Changing Legal Landscape and Public Health Implications

As of the podcast recording, 38 US states had implemented medical cannabis policies, with 24 states legalising recreational use. This shifting legal landscape has contributed to increased cannabis use overall, creating what Dr Hill described as a situation where “the train’s left the station.”

However, legal availability should not be confused with medical safety or efficacy. The rise in cannabis use has coincided with increases in cannabis use disorder, emergency department visits related to cannabis, and various other adverse outcomes.

Clinical Guidance for Healthcare Professionals

Healthcare professionals must balance acknowledging patient autonomy with providing evidence-based guidance about the therapeutic use of cannabis. Key points for clinical discussions include the limited scope of FDA approvals for cannabinoid medications, the lack of robust evidence for most conditions people treat with cannabis, the significant risk of developing cannabis use disorder (affecting roughly one-third of users), the particular dangers for young people whose brains are still developing, and the inadequacy of current treatments for cannabis use disorder.

Dr Hill noted that whilst many adverse effects exist, addiction itself is on the rise, and the medical community lacks effective treatments for cannabis use disorder. This reality makes prevention all the more critical.

Understanding the Risks

The therapeutic use of cannabis and cannabinoids represents a complex intersection of patient demand, limited scientific evidence, changing social attitudes, and concerning health risks. Whilst three FDA-approved cannabinoid medications exist for specific conditions, widespread cannabis use for medical purposes extends far beyond these narrow indications.

The dramatic increase in cannabis potency over recent decades, combined with rising rates of cannabis use disorder, creates a public health challenge that demands attention. Healthcare professionals must remain informed about both the limited evidence supporting medicinal cannabis and the well-documented risks associated with regular consumption.

For young people in particular, the potential for lasting cognitive impairment and the high risk of developing addiction make cannabis use a serious concern. As legal barriers continue falling, the importance of education about risks becomes paramount.

Understanding these realities allows healthcare professionals to engage patients in meaningful, evidence-based discussions about the therapeutic use of cannabis. Such conversations must acknowledge patient suffering and desire for relief whilst honestly presenting the limited evidence base and substantial risks that accompany cannabis consumption.

(Source: WRD NEWS)

Recent national policy changes have made cannabis increasingly available for medical purposes across numerous conditions. Yet a significant gap exists between what’s approved for cannabis therapeutic use and what scientific evidence actually supports. Understanding this distinction is crucial for public health and informed decision-making.

The FDA Approval Reality for Cannabis Therapeutic Use

Despite widespread availability of medical cannabis in dispensaries, the FDA has approved only three cannabis-related medications. Two are synthetic forms of delta-9-THC (dronabinol and nabilone), approved since the 1980s for treating nausea and appetite loss in AIDS and chemotherapy patients. The third, Epidiolex, contains highly purified cannabidiol (CBD) and treats severe childhood epilepsy.

These medications underwent rigorous randomised, placebo-controlled trials—the gold standard required of every prescription medicine. In contrast, the cannabis available at dispensaries has bypassed this scientific process entirely. Notably, even these FDA-approved medications have extremely narrow, specific applications and are not appropriate for the broad range of conditions for which dispensary cannabis is marketed.

Medical Cannabis Research: Significant Limitations

Dr Margaret Haney, director of Columbia University’s Cannabis Research Laboratory, highlights a critical problem: “Our societal changes have far exceeded placebo-controlled evidence.” Researchers face substantial barriers when studying cannabis therapeutic use due to its Schedule 1 classification, which requires extensive licensing and restricts available products for research.

This means scientists cannot simply purchase products from dispensaries to study their effectiveness. Instead, they’re limited to federally approved sources, creating a disconnect between what researchers can study and what patients actually use.

The Placebo Effect Challenge

Pain, anxiety, and sleep difficulties—the most common reasons people seek cannabis for medicinal purposes—are also the conditions most susceptible to placebo effects. When expectations are high, the brain can produce genuine symptom relief regardless of treatment content.

Studies examining cannabis therapeutic use consistently show this pattern. In one trial of women with chemotherapy-induced nerve pain, both the cannabis group and placebo group showed identical improvements. Pain ratings decreased significantly over eight weeks in both conditions, yet cannabis provided no additional benefit beyond placebo.

Cannabis Use Disorder: An Underestimated Risk

Approximately 5.8% of the population meets criteria for cannabis use disorder. When used daily for medical purposes, risk factors multiply. Users seeking cannabis therapeutic use develop higher rates of cannabis use disorder compared to those without chronic conditions, particularly when treating pain, anxiety, or depression.

Individuals with existing psychiatric diagnoses face double the risk of developing cannabis use disorder. Moreover, concurrent cannabis use worsens treatment outcomes for both the psychiatric condition and the substance use disorder itself—yet anxiety and depression remain leading reasons people seek medicinal cannabis despite minimal supporting evidence.

The therapeutic dose often produces intoxication, and repeated daily use increases dependency risk. Over 80% of medicinal cannabis users also use it recreationally, blurring the line between medical necessity and problematic use.

Cannabis Withdrawal: A Real Phenomenon

Daily cannabis users experience withdrawal symptoms when stopping, including:

• Severely disrupted sleep with increased nightmares
• Dramatic decrease in appetite
• Increased anxiety and irritability
• Depressed mood and restlessness

These symptoms can last weeks, with sleep disruption being particularly persistent. Many users believe they “need” cannabis to sleep or eat, when they’re actually experiencing withdrawal symptoms from dependency.

Anaesthesiologists report concerning patterns amongst daily cannabis users undergoing surgery. Patients arriving in acute withdrawal often experience heightened anxiety and increased pain sensitivity, requiring additional anxiolytic medication even before entering the operating theatre. Yet no evidence-based protocols exist for managing pre-surgical cannabis cessation—some physicians recommend stopping the morning of surgery, others suggest a month beforehand, but no data guides these decisions.

The State-by-State Confusion

Unlike other medications, cannabis regulations vary dramatically by state. The same condition deemed treatable with cannabis in one state may not qualify in a neighbouring state. This political approach to medicine means elected officials, rather than scientific evidence, determine what constitutes effective treatment for cannabis therapeutic use.

Healthcare providers face an impossible situation. They lack dosing guidelines, delivery method recommendations, or evidence-based protocols for different conditions. There’s no reliable information about THC-to-CBD ratios, appropriate concentrations, or how to address risks in vulnerable populations.

What We Actually Know

Whilst laboratory studies suggest cannabis may affect pain sensitivity and appetite under highly controlled conditions, these findings have consistently failed to translate into real-world clinical benefits.

The body possesses its own endocannabinoid system—natural cannabis-like compounds that regulate stress, pain, mood, and appetite. Cannabis overwhelms this delicate system in ways the body’s natural compounds never would. When people use cannabis daily, the brain attempts to adapt by reducing cannabinoid receptors, leading to tolerance.

Crucially, tolerance develops differently across effects. In studies with HIV patients, cannabis initially increased caloric intake significantly, but by day nine, this therapeutic benefit disappeared entirely—whilst intoxicating effects remained unchanged. This creates a troubling scenario where users must increase doses to maintain symptom relief, yet continue experiencing intoxication.

Some studies reveal cannabis worsening targeted symptoms. Research on obsessive-compulsive disorder found both high-THC and high-CBD cannabis increased anxiety rather than reducing it. The neuropathic pain trial showed sleep quality was actually worse in the cannabis group compared to placebo.

Route of administration significantly impacts risk. High-potency THC oils in vaporisers and “dabs” (over 85% THC) carry substantially greater dependency risk than traditional cannabis flower. When Dr Haney began her research, cannabis contained approximately 2% THC; today’s dispensary products reach 25-30% THC.

Sex differences also matter significantly. Women show greater sensitivity to cannabis’s pleasurable effects and withdrawal symptoms, yet demonstrate reduced pain relief compared to men at equivalent doses. This suggests optimal dosing may differ substantially between sexes, though current guidance doesn’t account for this.

The Path Forward

Evidence-based medicine requires randomised, placebo-controlled trials with products of known composition. Until such evidence exists, claims about cannabis therapeutic use effectiveness remain largely unsubstantiated.

The current situation represents a billion-dollar industry operating without the scientific foundation required of every other medication. Medical benefit has become whatever marketers claim it to be, with no obligation to prove effectiveness through controlled trials.

Much of what’s marketed as medicinal cannabis relies on expectation rather than pharmacology. The public deserves accurate information about both potential benefits and genuine risks, including cannabis use disorder, withdrawal symptoms, tolerance development, and the lack of dosing guidance. Making informed decisions about cannabis therapeutic use requires understanding what science has—and hasn’t—proven, and recognising that current evidence does not support the widespread medical claims being made.

(Source: WRD News)

Key Points

Question  What is the size of the placebo response in cannabinoid trials for clinical pain, and is the magnitude of placebo response associated with media attention on the trials?

Findings:  This meta-analysis of 20 studies of 1459 individuals found a significant pain reduction in response to placebo in cannabinoid randomized clinical trials. Media attention was proportionally high, with a strong positive bias, yet not associated with the clinical outcomes.

Meaning:  These findings suggest that placebo has a significant association with pain reduction as seen in cannabinoid clinical trials, and the positive media attention may shape placebo responses in future trials.

Abstract

Importance:  Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements.

Objective:  To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention.

Main Outcomes and Measures:  Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g).

Results:  Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q₁ = 5.47; I² = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes.

Conclusions and Relevance:  Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief. (Source: JAMA Open Network)

Also see

• Cannabis & Pain – Media Hype & the Placebo Reality?
• EXPOSE on CBD Part 2: Take Care with This Cannabinoid – The Problem of Pain
• CBD Not Recommended for Pain – Again (The placebo works)

Mounting scientific evidence continues to challenge the narrative that cannabis is a harmless substance, with alarming new research demonstrating significant THC effects on fertility and embryonic development.

A groundbreaking study conducted by researchers in Canada and Israel has uncovered disturbing links between THC exposure and chromosomal abnormalities in human embryos created through IVF. The findings add to growing concerns about the drug’s impact on reproductive health at a time when cannabis use amongst pregnant women is reportedly increasing.

Chromosomal Chaos

The research team’s analysis revealed that embryos exposed to THC experienced widespread genetic disruption. When comparing treated embryos to controls, scientists identified 89 genes that became overactive and 227 genes that became suppressed—clear evidence of substantial biochemical interference.

Higher THC concentrations proved even more damaging, with 402 genes showing increased activity and 62 displaying reduced function. These dramatic shifts in genetic expression suggest that the cannabis impact on reproduction extends deep into cellular processes critical for healthy development.

Perhaps most concerning, the study documented a 9% increase in aneuploidy—a condition where embryos possess an incorrect number of chromosomes. This abnormality frequently prevents successful conception or leads to developmental problems. The research also found that THC exposure elevated the likelihood of complex aneuploidy, involving the gain or loss of multiple chromosomes simultaneously.

Male Fertility Under Threat

These findings complement well-established research demonstrating THC effects on fertility in men. A comprehensive 2019 systematic review examined chronic cannabis users and found striking correlations between consumption frequency and sperm quality.

Men smoking cannabis 10 or more times weekly showed significantly lower sperm counts compared to those using it 5 to 9 times per week, suggesting a dose-dependent relationship. A Danish study involving 1,215 participants reinforced these conclusions, revealing that weekly cannabis users had 28% lower sperm concentration and 29% lower total sperm count than non-users.

Epigenetic Concerns Mount

This summer, researchers uncovered evidence that cannabis use can permanently alter DNA expression through methylation—the addition of methyl groups to DNA molecules. This process can affect how genes function without changing the underlying genetic code itself, potentially passing consequences to future generations.

The cannabis impact on reproduction now appears to operate through multiple mechanisms, from direct chromosomal damage to epigenetic modifications that may have long-lasting effects.

Vulnerable Populations at Risk

The Wall Street Journal recently highlighted a troubling trend: increasing numbers of pregnant women turning to marijuana to manage pain and anxiety. Ironically, robust scientific data indicates that cannabis actually exacerbates both conditions rather than alleviating them.

This disconnect between perception and reality reflects the success of industry marketing efforts that have positioned cannabis as a natural, safe alternative to conventional treatments. The consequences of this messaging are now becoming apparent, with expectant mothers potentially exposing their developing babies to significant harm.

A Growing Body of Evidence

The latest research on THC effects on fertility represents just one piece of an increasingly worrying puzzle. Scientific studies have now documented cannabis-related harm across multiple organ systems, including the brain, heart, lungs, and the genetic mechanisms that control cellular function.

The cumulative evidence paints a picture starkly different from the “safe and natural” image promoted by commercial interests. For couples planning to conceive, individuals undergoing fertility treatment, and pregnant women, the message from science is becoming unmistakably clear: cannabis poses serious risks to reproductive health and embryonic development.

The Path Forward

As cannabis legalisation expands across various jurisdictions, the importance of evidence-based public health messaging has never been greater. The recent findings regarding the cannabis impact on reproduction underscore the urgent need for comprehensive education about the drug’s genuine risks, particularly for those of reproductive age.

Healthcare providers working with patients considering pregnancy or undergoing fertility treatment must be equipped with current research to offer informed guidance. The romantic notion of cannabis as a benign natural remedy simply cannot withstand scientific scrutiny, especially when the health of future generations hangs in the balance.

The latest study examining THC effects on fertility serves as a stark reminder that what we put into our bodies can have profound consequences—not just for ourselves, but for the children we hope to bring into the world.

Source: The Drug Report

Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis.

Findings: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01–1·29, for less frequent cannabis use; and 1·17, 1·03–1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09–1·35; and 1·14, 1·03–1·26), lower pain self-efficacy scores (0·97, 0·96–1·00; and 0·98, 0·96–1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03–1·12; and 1·10, 1·06–1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation.

Interpretation: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain.

(Source: The Lancet – Public Health  https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30110-5/fulltext)

Also see

• Cannabis and Pain – Helpful – What is the Evidence?
• Academic concerns around Cannabis and Pain Management