Effects of delta-9 tetrahydrocannabinol and cannabidiol on cognitive outcomes following acute use of cannabis for chronic pain

In a study of 183 adults using edible cannabis for chronic low back pain, researchers found no significant acute changes in executive function, episodic memory, or processing speed after cannabis use. Participants using CBD-dominant products performed better on working memory than those using CBD + THC one hour after use, while the CBD group also showed more stable verbal-learning scores than participants using THC or mixed CBD/THC products. The findings add useful evidence to the discussion of how different cannabinoid profiles may affect cognition when cannabis is used for chronic pain.

Rationale: An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition.

Objectives: In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects on executive function, processing speed, memory, and verbal learning following acute use for chronic, non-specific low back pain.

Methods: Participants were in one of three self-selected edible cannabis groups: a) CBD-dominant, b) THC-dominant, or c) a mixed ratio of CBD to THC and completed a battery of cognitive tasks at pre-use, 1 h post-use use, and 2 h post-use.

Results: Among 183 participants (56.8% female; Mage = 45.6), those in the group using CBD outperformed participants using CBD + THC 1 h post use in working memory and produced more stable scores in verbal learning after use than participants using THC or CBD + THC. Additionally, while older age was associated with better working memory in the CBD group before use, that relationship was progressively attenuated over the subsequent timepoints. There were no significant effects of cannabis use on cognition in the domains of executive function, episodic memory, or processing speed.

Conclusions: Given the ubiquity of cannabis use for chronic pain and the ongoing call for more data, this study is relevant for informing clinical guidance on whether, and how, cannabis could be used in this context. In particular, understanding the acute impact on cognition from cannabis is critical, as cognitive functioning directly affects patients’ daily lives and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/42678518

“In summary, these findings support CBD’s potential to preserve cognitive performance in the context of chronic pain, contrasting with the more variable effects of THC across cognitive domains. The observed influence of age, particularly among those using CBD, suggests that both cannabinoid composition and individual factors shape cognitive outcomes following acute cannabinoid use.”

https://link.springer.com/article/10.1007/s00213-026-07157-x

Cannabinoid efficacy for pain: dose, chronicity and route

Cannabinoid pain relief depends on more than whether THC or CBD is used. Dose, route of administration, treatment duration and the type of pain can all influence whether a cannabis-based therapy provides meaningful analgesia or produces unwanted effects. This review examines those variables across preclinical and clinical research, while also considering the independent and combined roles of cannabis-derived terpenes.

Cannabis-based therapies are widely used for chronic pain, yet their mechanisms and therapeutic windows remain incompletely defined. This review synthesizes preclinical and clinical evidence on how dose, route of administration, treatment duration, and chemical composition shape analgesic efficacy and adverse-effect liability for Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and select cannabis-derived terpenes.

Across rodent pain models, acute THC reliably produces antinociception, but its therapeutic window is narrow because analgesic doses overlap with CB1 receptor-mediated side effects such as sedation, hypothermia, hyperphagia, and motor impairment. Repeated THC exposure leads to tolerance and dependence.

In contrast, CBD shows limited acute efficacy in naïve and inflammatory models but demonstrates more consistent benefit with repeated dosing in neuropathic and chemotherapy-induced pain, often without cannabimimetic adverse effects.

Terpenes such as linalool, β-caryophyllene, myrcene, limonene, α-terpineol, and α-bisabolol exhibit independent antinociceptive and anti-inflammatory properties and are thought to pharmacologically interact with cannabinoids in a dose-, ratio-, and route-dependent “entourage” effect that either enhance or constrain therapeutic benefit.

This review also focuses on integrating machine learning-based behavioral phenotyping of rodents to refine cannabinoid analgesia preclinical research. Computer vision pose-estimation and unsupervised clustering approaches enable high-resolution quantification of spontaneous and evoked natural behaviors, allowing the analytical dissociation of true analgesia from sedation, ataxia, or reduced exploration. By coupling these behavioral pipelines with pharmacokinetic and circuit-level analyses, emerging frameworks will define therapeutic windows with greater precision and improve the translational relevance of cannabinoid-based pain therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42661783

“Cannabinoid-based therapeutics are among the most widely used treatments for pain indications, with nearly one-third of adults with chronic pain using Cannabis for pain management.”

“Taken together, the studies reviewed here demonstrate that the analgesic efficacy of THC, CBD, and Cannabis-derived terepenes is dependent on dose, route of administration, treatment chronicity, and chemical composition.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1888863/full

Cannabis-Based Nanolipid Formulations for Pain Management

Cannabinoids such as CBD and THC show promising analgesic effects, but poor stability and bioavailability can limit their therapeutic performance. This review found that nanoencapsulation may improve cannabinoid stability, delivery, and pain-relieving potential across acute, chronic, and neuropathic pain models. The authors concluded that cannabinoid nanoformulations could help support the development of more stable, safe, effective, and accessible therapies, particularly for chronic and neuropathic pain.

“Medicinal cannabis has gained increasing attention from both the scientific community and clinical practice, due to the therapeutic potential of its major phytocannabinoids, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), for pain management.

This review compiled and analyzed the available evidence regarding the antinociceptive effects of nanoencapsulated cannabinoids compared to free compounds. The published works have explored some pharmaceutical formulations and administration routes on different acute, chronic and neuropathic pain experimental models.

The findings indicated that cannabinoids exhibited promising analgesic effects, while nanoencapsulation could enhance its stability and bioavailability.

Despite these advances, the number of reports investigating nanostructured cannabinoid-based systems remains limited, with a predominance of preclinical research. A recurrent lack of structural information and quality control data for such works was also noted. Furthermore, there were not identified any research regarding the nanoencapsulation of full-spectrum cannabis oils or whole cannabis extracts, highlighting a significant gap in the current literature.

Overall, nanoencapsulation emerges as a versatile strategy to overcome the intrinsic limitations of cannabinoids and expand its clinical applicability for pain treatment. Nevertheless, further efforts are required to determine standardized methodologies, facilitating the translation of preclinical findings into clinical practice, in order to provide stable, safe, effective and more accessible cannabinoid-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/42514922

“Overall, advances in the nanoencapsulation of cannabinoids and other cannabis-derived products can significantly contribute to the development of stable, safe, effective and cost-effective pain therapies, particularly for chronic and neuropathic pain conditions.”

https://www.mdpi.com/1999-4923/18/7/844


Lower Pain Intensity Is Associated with the Use of Recreational Edible Cannabis Products Containing Delta-9-Tetrahydrocannabinol: A Secondary Analysis in Adults Self-Managing Their Chronic Low Back Pain

Adults using edible cannabis products to self-manage chronic low-back pain reported lower pain intensity on days they used products containing THC. Over 14 days, pain also declined among participants using products with relatively equal amounts of THC and CBD, with 36.6% achieving at least a 30% reduction in pain intensity. The researchers concluded that lower daily pain was associated specifically with THC-containing products, while higher CBD doses may attenuate some of THC’s pain-relieving association.

Background/Objectives: Current literature regarding the efficacy of cannabis to reduce chronic pain intensity is mixed. Despite growing accessibility throughout the U.S., it is still unclear if the naturalistic use of recreational cannabis edible products is associated with decreases in pain intensity on days of use or longitudinally, and if these associations are dependent on the doses of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being consumed. 

Methods: The trial (NCT03522324) from which these data were pulled was pre-registered in April 2018. Participants (N = 243; 56% female; mean age = 46 ± 12 years) with self-reported chronic low-back pain selected a recreational edible cannabis product to use exclusively, ad libitum, for 14 days. Labeled THC and CBD potency were used to determine product group: CBD-dominant (n = 97), THC + CBD (n = 112), or THC-dominant (n = 34). Participants completed daily surveys indicating current pain intensity (PROMIS; 0-10 scale), use or non-use of their product, and cannabinoid dose (THC and CBD). 

Results: Linear mixed effects showed a significant use × group interaction (p = 0.002), indicating that pain intensity was significantly lower on days of use in THC-dominant (b = -0.66, 95% CI [-0.94,-0.37]) and THC + CBD (b = -0.41, 95% CI [-0.57,-0.25]) groups compared to days when cannabis was not used. A significant group × time interaction (p = 0.02) indicated that pain intensity significantly decreased from day 1 to day 14 in those using THC + CBD products (b = -0.05, 95% CI [-0.07,-0.03]), with 36.6% of participants in the THC + CBD group experiencing ≥30% reduction in pain intensity from day 1 to day 14. Increasing doses of THC (b = -0.02, 95% CI [-0.04, -0.01]), not CBD (b = 0.003, 95% CI [-0.03, 0.01]), were associated with significantly lower pain intensity on days following product use, with increasing doses of CBD diminishing the impact of THC dose (b = 0.02, 95% CI [0.01, 0.04]). 

Conclusions: These findings indicate a complex relationship between THC, CBD, and pain intensity associated with the naturalistic use of recreational cannabis edible products. Lower daily pain intensity was associated with the use of products containing THC; however, dose models indicate that this association may be attenuated at higher doses of CBD. Additionally, only products containing relatively equal amounts of THC and CBD were associated with lower pain intensity after 14 days of observation.”

https://pubmed.ncbi.nlm.nih.gov/42512114

“Daily data collected over 14 days of naturalistic cannabis use demonstrated that reductions in participants’ current pain intensity were associated with the use of cannabis edible products, but only in products that contained THC. More frequent use of these products in the previous 24 h was associated with improved reductions in pain intensity.”

https://www.mdpi.com/2227-9059/14/7/1642


Cannabidiol in the anterior insular cortex attenuates chronic neuropathic pain and comorbid anxiety- and depression-like behaviors: involvement of CB1 and 5-HT1A receptor signaling

Chronic neuropathic pain often occurs alongside anxiety and depression, making treatment more difficult than addressing pain alone. In this preclinical study, researchers examined CBD activity within the anterior insular cortex, a brain region involved in pain perception and emotional processing. CBD reduced neuropathic pain while also improving anxiety- and depression-like behaviors, with the effects linked to CB1 and 5-HT1A receptor signaling. The findings suggest that CBD may influence overlapping neural pathways involved in both chronic pain and its emotional consequences, supporting further investigation of cannabinoid-based approaches for complex pain conditions.

Background: Chronic neuropathic pain (NP) is frequently accompanied by anxiety- and depression‑like symptoms, reflecting maladaptive interactions between nociceptive and affective brain networks. The anterior insular cortex (AIC) integrates sensory and emotional dimensions of pain and represents a potential target for pharmacological modulation. Cannabidiol (CBD) exhibits analgesic and anxiolytic/antidepressant‑like properties through interactions with endocannabinoid and serotonergic systems.

Objectives: We investigated whether CBD microinjection into the AIC modulates NP and its affective comorbidities, and whether these effects depend on CB1 and 5‑HT1A receptors.

Methods: Male Wistar rats were subjected to chronic constriction injury (CCI) of the sciatic nerve. Fourteen days later, guide cannulae were implanted into the AIC. On day 21 post‑CCI, animals received intra‑AIC microinjections of CBD (15, 30, or 60 nmol/200 nL) or vehicle. Mechanical (von Frey test) and cold (acetone test) allodynia, anxiety‑like behavior (open field and elevated plus maze tests), and depression‑like behavior (forced swim and sucrose spray tests) were assessed by different psychobiological tests. The role of cannabinoid and serotonergic receptors was addressed by intra‑AIC pretreatment with either the CB1 receptor antagonist AM251 or the 5‑HT1A receptor antagonist WAY-100,635 in independent groups.

Results: AIC pretreatment with CBD dose‑dependently reduced mechanical and cold allodynia and anxiety‑ and depression‑like behaviors, with the most robust effects observed at 60 nmol. AIC Pretreatment with either AM251 or WAY-100,635 abolished the antinociceptive and affective effects of CBD.

Conclusion: CBD administration within the AIC produces integrated analgesic, anxiolytic, and antidepressant-like effects in a model of neuropathic pain. These effects are consistent with the involvement of CB1 and 5-HT1A receptor signaling. The findings identify the AIC as a relevant cortical substrate linking nociceptive and affective processes and support CBD as a promising psychopharmacological strategy for NP associated with emotional comorbidities.”

https://pubmed.ncbi.nlm.nih.gov/42390818

“In conclusion, this study demonstrates that CBD microinjection into the AIC attenuates mechanical and cold allodynia while also reducing anxiety- and depression-like behaviors in an experimental model of NP.”

“Overall, these findings highlight the AIC as a potential neural substrate involved in the interaction between chronic pain and its emotional comorbidities and identify CBD as a promising psychopharmacological approach for NP conditions associated with affective dysfunction.”

https://link.springer.com/article/10.1007/s00213-026-07116-6

Long-Term Inhaled Cannabis Therapy for Chronic Low Back Pain: A Five-Year Retrospective Analysis of Prospectively Collected Patient-Reported Outcomes in 241 Treatment-Refractory Patients

Chronic low back pain can remain difficult to control even after years of conventional treatment. This five-year analysis followed 241 treatment-refractory patients using inhaled medical cannabis and found sustained improvements in patient-reported pain and related outcomes over long-term follow-up. The study is notable for its duration and real-world clinical setting, offering a much longer view than most cannabis pain research. The findings suggest that inhaled cannabis may provide durable benefit for some patients with chronic low back pain who have not responded adequately to standard therapies.

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. 

Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4-22%, CBD 2-22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1-5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T2 provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan-Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. 

Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS -5.36 (95% CI -5.65, -5.07), ODI -17.68 (95% CI -19.73, -15.63), BPI-S -6.73 (95% CI -6.99, -6.47), and BPI-I -3.41 (95% CI -3.65, -3.16); all four contrasts had |z| ≥ 16.9 and p < 10-20. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T2 was F(4, 232) = 872.8, p < 10-20. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10-69), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = -0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05-1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022-2024, with patients returning to in-person follow-up by Year 4-5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54-0.60; BWV AUC 0.51). 

Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile-ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden-supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials.”

https://pubmed.ncbi.nlm.nih.gov/42351683

“Inhaled medical cannabis has emerged as a candidate analgesic for refractory chronic-pain syndromes.

Mechanistically, exogenous Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate the endocannabinoid system through CB1- and CB2-receptor signaling, with downstream effects on descending pain modulation, peripheral nociceptor sensitization, and affective dimensions of suffering.”

 “These data support consideration of inhaled cannabis as a potentially clinically meaningful, opioid-sparing option for patients who have failed conventional multimodal therapy.”

https://www.mdpi.com/2227-9059/14/6/1255

Self-reported cannabis use to manage opioid withdrawal symptoms and reductions in opioid use among people who use unregulated opioids: a cross-sectional analysis

As the opioid crisis continues, researchers are examining whether cannabis may play a role in reducing withdrawal symptoms or helping some people decrease opioid use. In this cross-sectional study of people using unregulated opioids, many participants reported using cannabis specifically to manage withdrawal-related symptoms, and some also reported reductions in opioid consumption. The findings add real-world evidence that people are already using cannabis as a self-directed strategy during opioid withdrawal. The study supports further research into whether cannabinoid-based approaches could have a formal role in harm reduction or opioid-use treatment.

Background: Opioid withdrawal is a significant challenge for people seeking to reduce or eliminate opioid use, and unmanaged withdrawal increases the risk of relapse and overdose. Using cannabis to manage opioid withdrawal has been reported by people who use opioids, yet it is not clear whether this leads to reductions in opioid use. Moreover, because pain is prevalent among people who use unregulated opioids (PWUO) and may contribute to ongoing opioid use, the effects of cannabis use to manage withdrawal symptoms may differ among individuals experiencing moderate to severe pain. We investigated the relationship between cannabis use to manage unregulated opioid withdrawal and self-reported reductions in opioid use among PWUO.

Methods: Data were derived from a cross-sectional questionnaire administered to cannabis-using PWUO in Vancouver, Canada, between December 2019 and November 2021. Multivariable logistic regression estimated the associations between cannabis use for opioid withdrawal and self-reported reductions in opioid use. A sub-analysis explored if these associations varied among participants living with and without moderate to severe pain.

Results: Among 197 participants, 89 (45.2%) reported cannabis use to manage symptoms of opioid withdrawal in the past six months. In multivariable analysis, cannabis use for opioid withdrawal was significantly associated with self-reported reductions in opioid use (adjusted Odds Ratio [AOR] = 2.16, 95% Confidence Interval [CI]: 1.13-4.19) in the same time period. In a sub-analysis, this association was only significant among participants with moderate to severe pain (AOR = 6.55; 95% CI: 2.44-19.63).

Conclusions: We observed a significant association between self-reported use of cannabis to manage unregulated opioid withdrawal and reductions in opioid use among cannabis-using PWUO living with pain. Aligned with other studies, these findings support conducting experimental trials of cannabinoids to support individuals experiencing opioid withdrawal and living with pain.”

https://pubmed.ncbi.nlm.nih.gov/42343486

https://link.springer.com/article/10.1186/s42238-026-00458-0

Development and clinical evaluation of a nanoemulsion for buccal delivery of cannabis extract in refractory chronic pain

For patients with refractory chronic pain, one challenge with cannabis-based treatment is achieving reliable absorption while avoiding the variability associated with oral or inhaled products. In this study, researchers developed a nanoemulsion designed for buccal delivery of cannabis extract and evaluated it clinically in patients with difficult-to-treat chronic pain. The formulation was intended to improve cannabinoid absorption through the lining of the mouth, and the clinical findings showed meaningful improvements in pain-related outcomes with acceptable tolerability. The results suggest that nanoemulsion-based buccal delivery may offer a more controlled and practical way to administer cannabis extracts for chronic pain.

“Cannabinoid-based therapies have gained increasing attention for the management of chronic and treatment-resistant pain, although their clinical application is limited by the poor aqueous solubility and variable bioavailability of Δ9-tetrahydrocannabinol (THC).

In this study, we developed and characterized a nanoemulsion (THC-NE) for buccal administration of a Cannabis sativa L. extract (Bedrocan®), with the aim of improving solubility, stability and bioavailability.

The optimized formulation, composed of pharmaceutically acceptable excipients, showed a narrow droplet size distribution (DH ≈ 73 nm, PDI ≈ 0.2), a THC content consistent with the theoretical value (3.53 ± 0.56 mg/mL), and good physicochemical stability at 4°C for at least 90 days. The formulation maintained its properties upon extensive dilution in simulated buccal fluids and after spray nebulization, supporting its suitability for oromucosal delivery. In vitro release studies confirmed sustained THC release from THC-NE, whereas negligible release was observed from the oil extract, highlighting the role of nanoformulation in enhancing solubilization and controlled release.

An observational study was conducted in 18 patients with chronic pain unresponsive to standard treatments. After a median follow-up of 189 days, mean pain scores (NRS) decreased significantly from 8.6 ± 0.9 to 5.4 ± 2.8 (p < 0.001), with 83% of patients achieving a ≥ 20% reduction. Among responders, the mean NRS decreased by 45% and treatment persistence was found to be high, with 64% of patients still remaining under therapy after six months. A total of 17 adverse events were reported in 11 patients, most of which were mild to moderate and transient. Additionally, treatment interruption occurred in three patients due to adverse events, in other three owing to limited efficacy and in two for logistical reasons.

Overall, these findings indicate that buccal administration of THC-NE represents a promising patient-friendly approach for cannabis-based therapy, offering improved solubility, controlled release and meaningful clinical benefit in patients with refractory chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/42336000

“Among the bioactive compounds found in Cannabis sativa, Δ9-tetrahydrocannabinol (THC) has been identified as the primary psychoactive component, exhibiting significant analgesic, antispastic, and neuroprotective properties. “

“This study demonstrates that NE technology can be successfully applied to develop a stable and efficient buccal formulation of Cannabis sativa extract. The optimized THC-NE proved to be physicochemically stable, robust under dilution, and suitable for administration via standard spray devices, while ensuring enhanced release of THC compared to the oily extract.”

https://www.sciencedirect.com/science/article/pii/S0939641126001839?via%3Dihub

Case Report: Oral and topical chronic administration of THC-rich and CBD-rich cannabis oil as palliative care in a rescued horse with open wound, sarcoid and chronic pain

Cannabis-based treatments are also being explored in veterinary palliative care, particularly for animals with chronic pain and difficult-to-manage skin lesions. This case report describes a rescued horse with an open wound, sarcoid, and persistent pain that received both oral and topical THC-rich and CBD-rich cannabis oils over an extended period. The authors reported improvements in pain, wound condition, and overall comfort during treatment. As a single-animal case report, the findings suggest that cannabinoid-based therapies may deserve further study as supportive care options in veterinary patients with chronic wounds and pain.

“Cannabinoid-based therapies have shown analgesic, anti-inflammatory, and wound-healing potential across veterinary species; however, clinical data on long-term use of THC-rich formulations in horses remain scarce.

This case report describes the use of combined oral and topical THC-rich and CBD-rich full-spectrum cannabis oils as part of a palliative care strategy in a rescued horse with severe chronic disease.

A senior mixed-breed gelding was rescued with a large, chronic ulcerative lesion of the left hind limb, severe malnutrition, non-weight-bearing lameness (AAEP grade 5/5), and refractory pain. Diagnostic workup identified a fibroblastic equine sarcoid complicated by complete suspensory tendon rupture, early osteomyelitis, and chronic joint disease. Conventional medical and surgical options were limited due to poor response, disease severity, and resource constraints.

A long-term palliative protocol was initiated using oral THC-rich and CBD-rich full-spectrum cannabis oils (1:1 ratio; 100 mg/mL each) with gradual dose escalation to a target of 0.5 mg/kg of each compound every 12 hours. The same formulation was applied topically to the wound once to twice daily. Treatment duration was 10 months, with concurrent multimodal analgesia as needed.

Cannabinoid therapy was associated with sustained improvements in appetite, body condition, pain, and mobility. Marked wound improvement was observed, including reduced granulation tissue, improved epithelialization, and resolution of self-mutilation.

No clinically relevant adverse effects or laboratory abnormalities occurred during routine dosing. Transient ataxia and sedation were noted only at high rescue doses near end of life. Despite eventual disease progression and euthanasia due to refractory pain, quality of life was substantially improved for most of the treatment period.

This case supports the potential role of combined THC-rich and CBD-rich cannabis oils as a safe and effective adjunct in multimodal palliative care for horses with chronic, refractory conditions. Controlled studies are warranted to define optimal dosing and indications.”

https://pubmed.ncbi.nlm.nih.gov/42311392

“Across veterinary species, cannabinoids have shown therapeutic potential with favorable safety and tolerability profiles.”

“The aim of this case report is to describe a long-term multimodal clinical approach using cannabinoids (THC and CBD) in a rescued horse affected by a wound/sarcoid and joint disease, as part of a palliative care strategy for pain management, inflammation control, and wound-healing enhancement.”

“This case suggests that long-term administration of THC-rich and CBD-rich cannabis oils may be a useful adjunct for palliative management in horses with chronic, refractory conditions.”

“Cannabinoid therapy was associated with improved comfort, mobility, and quality of life, supporting its potential role within multimodal palliative care.”

https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2026.1794084/full


Benefits of Medical Cannabis in Patients With Pain Registered in the Minnesota Medical Cannabis Program

Real-world medical cannabis programs provide an important opportunity to examine how patients with chronic pain respond outside tightly controlled clinical trials. This analysis of participants in Minnesota’s Medical Cannabis Program found that many patients reported meaningful improvements in pain and related symptoms after beginning medical cannabis treatment. Benefits were also reflected in measures of daily functioning and quality of life, suggesting that cannabis may provide broader relief than pain reduction alone for some patients. The findings add large-scale, real-world evidence supporting the role of medical cannabis as a treatment option for people living with persistent pain

Purpose: Medical cannabis is commonly used to treat chronic pain. Clinical trials typically use only one type and dosage of medical cannabis product, which is not reflective of real-world use. The use of a state-run medical cannabis program can bridge the gap between clinical research and real-world use of medical cannabis to estimate the benefits of cannabis use on patient symptoms. This study aimed to describe medical cannabis use among patients with intractable and chronic pain in the Minnesota Medical Cannabis Program and estimate pain reduction benefits received from medical cannabis.

Methods: Patients who enrolled in the Minnesota Medical Cannabis Program between March 2022 and February 2023 for chronic pain and purchased medical cannabis for at least 8 months were included in this study. Patients were required to complete the Patient Self-Evaluation before each medical cannabis purchase, which included the PEG (Pain, Enjoyment of Life, and General Activity) scale. The main outcome of this analysis was a ≥30% change in PEG component score within 4 months of first medical cannabis purchase. The proportion of patients who maintained that reduction for an additional 4 months was also calculated. Medical cannabis product purchases were queried from the first 4 months in the program and categorized by route of administration and tetrahydrocannabinol:cannabidiol ratio. Medical cannabis purchasing profiles were created using k-means clustering to group patients who purchased similar proportions of product types. Adjusted logistic regression models were run to investigate the association between medical cannabis purchasing profile and reporting ≥30% reduction in PEG score.

Findings: Among patients reporting moderate-to-severe scores at program enrollment, 54.9% reported a ≥30% score improvement for life enjoyment, 54.7% reported improvement in general activity interference, and 40.8% reported improvement in pain score within 4 months of their first purchase. Cannabis flower products were most commonly purchased by patients. High tetrahydrocannabinol:cannabidiol products were the most commonly purchased in all medical cannabis product categories. K-means clustering created 5 product purchasing profiles, which were not associated with PEG score improvement outcomes after adjustment for number of purchasing transactions.

Implications: Medical cannabis patients report reduction in PEG scores within 4 months of first medical cannabis purchase using a variety of medical cannabis products. Future research on medical cannabis should determine the frequency of use of different products and administration methods to further investigate how cannabis can be used for effective pain management in patients with chronic pain.”

https://pubmed.ncbi.nlm.nih.gov/42303550

“Medical cannabis patients report improvement in pain symptoms after four months.”

https://www.clinicaltherapeutics.com/article/S0149-2918(26)00187-6/fulltext