Cannabis is now one of the most frequently discussed therapeutic agents in modern medicine, driven by expanding access programmes and a growing demand for alternatives to conventional pharmaceuticals. Among the most common reasons patients report using medical cannabis are pain, sleep disturbance, and anxiety.
While anecdotal reports have long described relief across these domains, clinical evidence paints a more nuanced picture.
More rigorous trials suggest modest improvements in pain and sleep quality, while evidence for anxiety remains limited and inconsistent. Understanding these distinctions is crucial as policymakers, prescribers, and industry leaders look to position cannabinoids within evidence-based frameworks.
Pain Relief: Small but Meaningful Gains for Some Patients
How Cannabis Influences Pain Pathways
The endocannabinoid system (ECS) plays a critical role in pain modulation through CB1 receptors in the central nervous system and CB2 receptors on immune cells. Δ9-tetrahydrocannabinol (THC) primarily activates CB1 receptors, reducing pain perception, while cannabidiol (CBD) exerts indirect effects that may modulate inflammation and attenuate hyperalgesia (an increased sensitivity to pain).
Together, these mechanisms explain why cannabinoids are explored as adjunct therapies for neuropathic pain, multiple sclerosis-related spasticity, and cancer pain, conditions where conventional analgesics often fall short.
Evidence from Clinical Trials
A landmark systematic review and meta-analysis published in The BMJ (Wang et al., 2021) examined 32 randomised controlled trials involving more than 5,000 adults using non-inhaled medical cannabis or cannabinoids for chronic pain. The analysis found small reductions in pain intensity (mean difference −0.50 cm on a 10-cm visual analogue scale) and small improvements in sleep quality (−0.35 cm) compared with placebo.
While these effects may not meet the minimally important difference (≈1 cm) for all patients, they nonetheless suggest clinically relevant benefits for subsets of individuals, particularly those with neuropathic or cancer-related pain.
Other studies, including those on nabiximols (Sativex) and dronabinol, have demonstrated reductions in neuropathic pain intensity, particularly in patients with multiple sclerosis or chronic pain (Dykukha et al., 2021).
However, evidence for sleep improvement remains inconsistent. A Neuropharmacology meta-analysis (Spanagel & Bilbao, 2021) found that approved THC-based cannabinoids such as dronabinol and nabilone showed no significant effect on sleep compared with placebo, while CBD similarly had no measurable impact.
These findings suggest that any perceived sleep benefits from combination products like Sativex may be secondary to pain relief rather than a direct sedative effect.
Balancing Efficacy and Adverse Events
The same BMJ review found an increased incidence of dizziness, drowsiness, nausea, and impaired attention compared with placebo. Dizziness risk appeared to increase with longer treatment duration. Importantly, these effects were transient and self-limiting, and serious adverse events were rare.
From a clinical standpoint, these findings support a cautious but positive view of cannabinoids in chronic pain management: small average benefits, offset by tolerable short-term risks.
Sleep: Subjective Improvements, Objective Ambiguities
Cannabinoids interact with sleep architecture by influencing sleep latency, REM cycles, and circadian rhythm through CB1-mediated modulation of neurotransmitters such as GABA and serotonin. THC often exerts acute sedative effects, while CBD may promote wakefulness or circadian stability, depending on dose and timing.
A 2022 review published in Sleep analysed 31 studies exploring cannabis and sleep outcomes. The authors found consistent improvements in subjective sleep quality, especially among individuals with chronic pain or PTSD, but limited evidence of objective improvements in polysomnography measures. No clear distinction emerged between THC- and CBD-dominant formulations, and study heterogeneity remained a challenge.
Similarly, the BMJ meta-analysis (Wang et al., 2021) observed small improvements in sleep quality among participants using non-inhaled cannabinoids for chronic pain. Stockings et al. (2018, PAIN) reported a modest but statistically significant reduction in sleep problems with nabiximols (Sativex) and other cannabinoid-based medicines compared with placebo, though the clinical importance was uncertain.
By contrast, a Neuropharmacology review (Spanagel & Bilbao, 2021) concluded that approved synthetic THC analogues such as dronabinol and nabilone show no measurable effect on sleep, while CBD alone appears similarly neutral. This suggests that any observed sleep benefits are likely secondary to pain relief rather than a direct hypnotic action.
In clinical settings, formulations combining THC and CBD (such as nabiximols-type extracts) are often better tolerated than high-THC products, largely due to CBD’s moderating effect on psychoactivity. However, no specific THC:CBD ratio has been clinically validated to optimise sleep outcomes. Current evidence remains limited and inconsistent, underscoring the need for standardised trials that measure both subjective and objective sleep metrics.
Anxiety: Therapeutic Potential with Major Caveats
The relationship between cannabis and anxiety is dose-dependent and biphasic. Consistent with preclinical models, low doses of THC may engage CB1 receptors to dampen anxiety, whereas higher doses reliably induce anxiety, tachycardia, and paranoia.
Human data now strongly support anxiogenic (anxiety triggering) effects of THC administration, especially in individuals with limited cannabis experience (Lichenstein 2022). Regular users, however, appear less sensitive to these effects, and co-administration with CBD may partially mitigate THC-induced anxiety.
CBD and Anxiolytic Mechanisms
CBD interacts with 5-HT1A serotonin receptors, TRPV1 ion channels, and the endocannabinoid system to influence emotional regulation. Yet findings remain inconsistent.
Earlier studies suggested that acute doses of 300–600 mg CBD reduced anxiety during public-speaking tasks, but more recent RCTs largely fail to replicate these effects in healthy participants.
According to Stanciu et al. (2021) and Lichenstein (2022), evidence from clinical populations is mixed:
- Small positive effects in adolescents with social anxiety and individuals with treatment-resistant anxiety.
- No significant effects in exposure-therapy augmentation or PTSD from sexual trauma.
- Possible benefit in substance-use disorders such as heroin or cannabis dependence, but not cocaine.
Overall, CBD’s anxiolytic profile appears dose- and population-specific, following a bell-shaped response curve where intermediate doses may be most effective.
Clinical Perspective
At present, cannabinoids cannot be considered first-line treatments for anxiety disorders. THC’s anxiogenic (anxiety-inducing) potential warrants caution, and while CBD shows promising acute or adjunctive effects, long-term data remain sparse and heterogeneous.
Further controlled studies are required to determine optimal dosing, sex-specific responses, and long-term efficacy before clinical recommendations can be made.
Regulatory and Clinical Context
Prescribing Frameworks and Global Access
United Kingdom 🇬🇧
Cannabis-based medicinal products (CBMPs) are available only through specialist clinicians and typically limited to treatment-resistant epilepsy, multiple sclerosis–related spasticity, and chronic pain. These are prescribed via private clinics or hospital specialists, with NHS access still extremely limited.
Under MHRA and NICE guidance, anxiety and insomnia are not recognised indications due to insufficient clinical evidence. However, private medical cannabis clinics report increasing off-label prescribing for these conditions, particularly using CBD-dominant formulations.
Germany 🇩🇪
Medical cannabis can be prescribed under Section 31(6) of the German Social Code (SGB V) for severe chronic pain, spasticity in multiple sclerosis, and palliative symptom management, reimbursable under statutory health insurance.
Following the CanG reform (2024), medical use remains legal and regulated under the Medicinal Cannabis Act, separate from adult-use frameworks.
Anxiety and sleep disorders are occasionally treated off-label, but remain unsupported by strong clinical evidence and subject to insurer scrutiny.
Canada 🇨🇦
Under the Cannabis Regulations (2018), medical cannabis can be authorised by healthcare practitioners for any condition they deem appropriate, resulting in broad clinical discretion.
Recent registry data (Health Canada, 2023) show that pain, sleep, and anxiety are among the top reported indications.
However, systematic reviews highlight low-to-moderate evidence quality and limited standardisation in dosing or formulation.
Australia 🇦🇺
Through the Therapeutic Goods Administration (TGA) Special Access Scheme (SAS-B) and Authorised Prescriber pathway, clinicians can prescribe medical cannabis for chronic pain, insomnia, and anxiety, among other conditions.
As of 2024, anxiety and sleep disorders rank among the top three reasons for prescription approvals, but the TGA explicitly states that evidence remains inconclusive and products are unapproved medicines.
The Evidence Gap
Despite the rapid expansion of medical cannabis programmes, regulators across jurisdictions consistently highlight the lack of high-quality, standardised clinical data.
Most existing studies are short-term, underpowered, and rely on subjective or self-reported outcomes, such as sleep quality or pain relief scores, which limit reproducibility. Few use validated clinical scales (e.g., PSQI for sleep, HAM-A for anxiety), and cross-study comparisons are complicated by differences in cannabinoid ratios, delivery methods, and dosing regimens.
The European Medicines Agency (EMA) and the UK MHRA have both noted that the majority of cannabis-based products are not authorised medicines because they have not demonstrated consistent efficacy through controlled phase III trials.
Similarly, Health Canada and Australia’s Therapeutic Goods Administration (TGA) categorise most formulations as unapproved or investigational, supplied under compassionate-use or special-access frameworks.
Encouragingly, a new wave of phase II and III randomised controlled trials is beginning to address these shortcomings.
Current registry data (ClinicalTrials.gov, EU Clinical Trials Register, accessed October 2025) show ongoing studies examining:
- Cannabidiol-Assisted Learning for Managing Generalized Anxiety Disorder (CALM)
- THC:CBD oral sprays and oils for chronic insomnia and pain-related sleep disturbance (Zelira Therapeutics, AusCann, Jazz Pharmaceuticals).
- Cannabinoids and Traumatic Brain Injury: A Randomized, Placebo Controlled Trial
These trials incorporate standardised dosing, placebo controls, and validated outcome measures, representing a shift toward the level of evidence regulators require for formal marketing authorisation.
However, until these results are published, the clinical evidence base remains fragmented—with most real-world prescribing still guided by observational data, patient-reported outcomes, and extrapolation from small-scale studies.
Risks, Benefits, and the Path Forward
The expanding clinical literature presents a cautious but consistent picture of cannabis-based therapeutics: measurable yet modest benefits, offset by limited standardisation and mixed safety outcomes.
Pain
Evidence from meta-analyses such as Wang et al. (BMJ, 2021) and Stockings et al. (PAIN, 2018) confirms that non-inhaled cannabinoids offer small but statistically significant reductions in pain intensity, particularly in neuropathic and cancer-related pain. The absolute improvements are modest—often below minimal clinically important thresholds—but can be meaningful for refractory patients when used adjunctively with other treatments.
Sleep
Short-term studies indicate subjective improvements in sleep quality, especially in individuals experiencing pain or PTSD-related insomnia. However, objective sleep measures show inconsistent changes, and long-term outcomes remain uncertain.
Spanagel & Bilbao (2021) found no measurable sleep benefit from approved THC or CBD monotherapies, suggesting observed improvements are likely secondary to pain reduction rather than a direct sedative effect.
Ongoing clinical trials exploring standardised THC:CBD formulations for insomnia may help clarify dose–response relationships and optimal cannabinoid ratios.
Anxiety
The evidence for cannabinoids in anxiety remains inconclusive.
Stanciu et al. (2021) and Lichenstein (2022) report that CBD shows mixed, short-term anxiolytic effects, whereas THC is more consistently anxiogenic, particularly in infrequent users or at higher doses.
While some studies demonstrate acute reductions in social or performance anxiety with moderate-dose CBD, replication failures and dose inconsistency limit clinical applicability.
Currently, no cannabinoid-based medicine is approved for anxiety, and long-term data are lacking.
Clinical and Commercial Implications
For clinicians and product developers alike, the emerging consensus is clear:
- Position cannabinoids as adjunctive, not primary, therapies.
- Emphasise short-term or condition-specific benefits (e.g., neuropathic pain relief, improved sleep continuity in pain cohorts).
- Communicate dose dependency, formulation differences, and interindividual variability transparently.
- Avoid broad efficacy claims, particularly around anxiety or mood disorders.
Adverse events such as dizziness, drowsiness, impaired attention, and nausea remain common but typically mild and reversible. These risks should be clearly disclosed—especially for older adults, polypharmacy patients, and individuals with mental health comorbidities.
Conclusion: Promise Tempered by Precision
Cannabinoids engage multiple physiological systems, producing effects that are highly context-dependent and influenced by dose, route, and patient profile.
Current data support modest benefits for pain and sleep, but the therapeutic role in anxiety remains unproven.
For clinicians, researchers, and industry stakeholders, the next phase of progress depends on rigorous, standardised clinical trials and pharmaceutical-grade formulation consistency.
The medical cannabis field is maturing, but enduring credibility will depend on a shift from market enthusiasm to evidence-driven precision—where efficacy claims are backed by reproducible science rather than anecdote.
Further Reading
Anxiety & Mood Disorders
Lichenstein, S.D. (2022). THC, CBD, and anxiety: A review of recent findings. Current Addiction Reports. https://doi.org/10.1007/s40429-022-00450-7
Stanciu, C.N., Brunette, M.F., Teja, N., Budney, A.J. (2021). Evidence for cannabinoids in mood disorders, anxiety disorders, and PTSD: A systematic review. Psychiatric Services. https://doi.org/10.1176/appi.ps.202000189
Bergamaschi, M.M., et al. (2011). Cannabidiol reduces anxiety induced by simulated public speaking in treatment-naïve social phobia. Neuropsychopharmacology. https://www.nature.com/articles/npp20116
Crippa, J.A., et al. (2009). Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. Journal of Psychopharmacology. https://pmc.ncbi.nlm.nih.gov/articles/PMC3079847/
Pain & Sleep
Wang, L., et al. (2021). Medical cannabis or cannabinoids for chronic pain: systematic review & meta-analysis. BMJ. https://www.bmj.com/content/374/bmj.n1034
Stockings, E., et al. (2018). Cannabis and cannabinoids for chronic non-cancer pain: systematic review & meta-analysis. PAIN. https://journals.lww.com/pain/fulltext/2018/10000/cannabis_and_cannabinoids_for_the_treatment_of.6.aspx
Spanagel, R., Bilbao, A. (2021). Approved cannabinoids for medical use: a practical guide for clinicians. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/34181977/
Babson, K.A., Sottile, J.E., Morabito, D. (2017). Cannabis, cannabinoids, and sleep: a review. Current Psychiatry Reports. https://link.springer.com/article/10.1007/s11920-017-0775-9
Suraev, A.S., et al. (2020). Cannabinoid therapies in sleep disorders: systematic review. Sleep Medicine Reviews. https://pubmed.ncbi.nlm.nih.gov/32603954/
Global Frameworks & Regulatory Context
This article is for informational purposes only and does not constitute medical advice. Individuals should consult a qualified clinician before initiating or modifying cannabis-based treatments.
