Chapter 6
EVIDENCE-BASED THERAPEUTIC APPLICATIONS
6.1 Introduction
Medical cannabis is increasingly recommended by health care providers as a beneficial medical therapy across a wide spectrum of conditions— chronic pain, anxiety/PTSD, epilepsy, neurologic conditions, inflammatory bowel disease, immune-mediated diseases and many others.
This chapter outlines recent high-level evidence—RCTs, meta-analyses, and observational studies—to guide physicians, pharmacists, and other healthcare professionals in making data-driven decisions. I encourage you to directly read and review these resources via public databases and libraries.
6.2 Chronic Pain
6.2.1 Clinical Context
As a pain specialist, I recognize the importance of noting that pain as an unpleasant sensory and emotional experience. The benefits of medical cannabis can extend to both by reducing pain intensity and helping to reduce anxiety, depression and/or PTSD. Common types of pain are lumbar pain, migraines, neuropathy, fibromyalgia, and cancer pain.
According to the CDC, approximately 50 million in the U.S. experience chronic pain.
In addition to other advanced therapies, consider medical cannabis to complement physical, interventional, medical, psychiatric, regenerative, and/or surgical treatments.
Clinical Insight: Begin therapy with a low THC:CBD ratio to reduce psychoactive side effects. Sublingual tinctures can offer precise dosing and a rapid onset compared to edibles. Allow patients to trial different routes and ratios to find the best combination for their individual needs.
6.2.2 Key References
Chronic Pain | Lumbar Pain
Hameed M, Prasad S, Jain E, Dogrul BN, Al-Oleimat A, Pokhrel B, Chowdhury S, Co EL, Mitra S, Quinonez J, Ruxmohan S, Stein J. Medical Cannabis for Chronic Nonmalignant Pain Management. Curr Pain Headache Rep. 2023 Apr;27(4):57-63. doi: 10.1007/s11916-023-01101-w. Epub 2023 Mar 10. PMID: 36897501; PMCID: PMC9999073.
Lee C, Danielson EC, Beestrum M, Eurich DT, Knapp A, Jordan N. Medical Cannabis and Its Efficacy/Effectiveness for the Treatment of Low-Back Pain: a Systematic Review. Curr Pain Headache Rep. 2023 Dec;27(12):821-835. doi: 10.1007/s11916-023-01189-0. Epub 2023 Dec 2. PMID: 38041708; PMCID: PMC11095816.
Bennici A, Mannucci C, Calapai F, Cardia L, Ammendolia I, Gangemi S, Calapai G, Griscti Soler D. Safety of Medical Cannabis in Neuropathic Chronic Pain Management. Molecules. 2021 Oct 16;26(20):6257. doi: 10.3390/molecules26206257. PMID: 34684842; PMCID: PMC8540828.
Jeddi HM, Busse JW, Sadeghirad B, Levine M, Zoratti MJ, Wang L, Noori A, Couban RJ, Tarride JE. Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials. BMJ Open. 2024 Jan 3;14(1):e068182. doi: 10.1136/bmjopen- 2022-068182. PMID: 38171632; PMCID: PMC10773353.
Arthritis
Vannabouathong C, Zhu M, Chang Y, Bhandari M. Can Medical Cannabis Therapies be Cost-Effective in the Non-Surgical Management of Chronic Knee Pain? Clin Med Insights Arthritis Musculoskelet Disord. 2021 Mar 16;14:11795441211002492. doi: 10.1177/11795441211002492. PMID: 33795939; PMCID: PMC7970188.
Paland N, Hamza H, Pechkovsky A, Aswad M, Shagidov D, Louria-Hayon I. Cannabis and Rheumatoid Arthritis: A Scoping Review Evaluating the Benefits, Risks, and Future Research Directions. Rambam Maimonides Med J. 2023 Oct 29;14(4):e0022. doi: 10.5041/RMMJ.10509. PMID: 37917863; PMCID: PMC10619990.
Migraines
Poudel S, Quinonez J, Choudhari J, Au ZT, Paesani S, Thiess AK, Ruxmohan S, Hosameddin M, Ferrer GF, Michel J. Medical Cannabis, Headaches, and Migraines: A Review of the Current Literature. Cureus. 2021 Aug 24;13(8):e17407. doi: 10.7759/cureus.17407. PMID: 34589318; PMCID: PMC8459575.
Sherpa ML, Shrestha N, Ojinna BT, Ravi N, Shantha Kumar V, Choday S, Parisapogu A, Tran HH, Kc A, Elshaikh AO. Efficacy and Safety of Medical Marijuana in Migraine Headache: A Systematic Review. Cureus. 2022 Dec 17;14(12):e32622. doi: 10.7759/cureus.32622. PMID: 36660507; PMCID: PMC9845509.
Neuropathy
Seevathee K, Kessomboon P, Manimmanakorn N, Luangphimai S, Thaneerat T, Wanaratna K, Plengphanich S, Thaenkham T, Sena W. Efficacy and Safety of Transdermal Medical Cannabis (THC:CBD:CBN formula) to Treat Painful Diabetic Peripheral Neuropathy of Lower Extremities. Med Cannabis Cannabinoids. 2024 Nov 14;8(1):1-14. doi: 10.1159/000542511. PMID: 39720705; PMCID: PMC11666268.
Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W. Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2018 Mar 7;3(3):CD012182. doi: 10.1002/14651858.CD012182.pub2. PMID: 29513392; PMCID: PMC6494210.
Fibromyalgia
Lopera V, Restrepo JC, Amariles P. Effectiveness and safety of cannabis-based products for medical use in patients with fibromyalgia syndrome: A systematic review. Explor Res Clin Soc Pharm. 2024 Oct 11;16:100524. doi: 10.1016/j. rcsop.2024.100524. PMID: 39498228; PMCID: PMC11533093.
Strand NH, Maloney J, Kraus M, Wie C, Turkiewicz M, Gomez DA, Adeleye O, Harbell MW. Cannabis for the Treatment of Fibromyalgia: A Systematic Review. Biomedicines. 2023 Jun 2;11(6):1621. doi: 10.3390/ biomedicines11061621. PMID: 37371716; PMCID: PMC10295750.
Cancer-related | Post-Chemotherapy
Häuser W, Welsch P, Radbruch L, Fisher E, Bell RF, Moore RA. Cannabis-based medicines and medical cannabis for adults with cancer pain. Cochrane Database Syst Rev. 2023 Jun 5;6(6):CD014915. doi: 10.1002/14651858. CD014915.pub2. PMID: 37283486; PMCID: PMC10241005.
Teoh D, Smith TJ, Song M, Spirtos NM. Care After Chemotherapy: Peripheral Neuropathy, Cannabis for Symptom Control, and Mindfulness. Am Soc Clin Oncol Educ Book. 2018 May 23;38:469-479. doi: 10.1200/EDBK_209437. PMID: 30231411.
6.3 Medical Cannabis and the Opioid Crisis
6.3.1 Clinical Context
The opioid epidemic remains a public health emergency. Overdose deaths in the United States have continued to rise while access for adequate pain relief and specialized mental health treatments remains in significant need.
Cannabis’s analgesic properties may allow clinicians to reduce opioid dosages, mitigating risk for dependence and fatal overdose.
Clinical Insight 1: Consider medical cannabis as a valuable tool to help reduce morbidity (burden of disease) and mortality (fatalities) in opioid-related complications.
Clinical Insight 2: Cannabinoids, unlike opioids and other narcotic medicines, do not suppress breathing centers in the brain stem and are considered by many pain specialists, a harm reduction strategy when used to reduce and/or replace substances that can cause fatal overdose.
Clinical Insight 3: Integrate cannabis into multimodal pain management as an opioid- sparing strategy. Emphasize systematic tapering protocols, close monitoring for sedation, and robust patient education on combined opioid-cannabinoid therapies.
6.3.2 Key References
Reduction in Opioid Use ( 65-74% reduction )
Okusanya BO, Asaolu IO, Ehiri JE, Kimaru LJ, Okechukwu A, Rosales C. Medical cannabis for the reduction of opioid dosage in the treatment of non- cancer chronic pain: a systematic review. Syst Rev. 2020 Jul 28;9(1):167. doi: 10.1186/s13643-020-01425-3. PMID: 32723354; PMCID: PMC7388229.
Jeddi HM, Busse JW, Sadeghirad B, Levine M, Zoratti MJ, Wang L, Noori A, Couban RJ, Tarride JE. Cannabis for medical use versus opioids for chronic non-cancer pain: a systematic review and network meta-analysis of randomised clinical trials. BMJ Open. 2024 Jan 3;14(1):e068182. doi: 10.1136/bmjopen- 2022-068182. PMID: 38171632; PMCID: PMC10773353.
6.4 Mental Health Applications: Anxiety, PTSD, and Depression
6.4.1 Clinical Context
Mental health has become increasingly recognized as an area where more awareness is needed, especially since the COVID pandemic and a variety of tragic events in the U.S. and other countries.
Health care providers can have a positive impact by raising awareness of effective treatments and directly or in-directly guiding patients to potential treatment options.
Clinical Insight: Anxiety/PTSD: Start with CBD-dominant formulations; consider adding small THC doses for PTSD if indicated. Monitoring: Screen regularly for paranoia or exacerbation of anxiety, especially if THC content is increased.
6.4.2 Key References for Anxiety | PTSD | Depression
Mechanism Anxiety and PTSD
Vitale RM, Iannotti FA, Amodeo P. The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets. Int J Mol Sci. 2021 May 5;22(9):4876. doi: 10.3390/ijms22094876. PMID: 34062987; PMCID: PMC8124847.
Perry RN, Ethier-Gagnon MA, Helmick C, Spinella TC, Tibbo PG, Stewart SH, Barrett SP. The impact of cannabidiol placebo on amygdala-based neural responses to an acute stressor. J Psychopharmacol. 2024 Nov;38(11):935-948. doi: 10.1177/02698811241287557. Epub 2024 Oct 14. PMID: 39400103; PMCID: PMC11528970.
Clinical Benefit in Anxiety and PTSD
Berger M, Amminger GP, McGregor IS. Medicinal cannabis for the treatment of anxiety disorders. Aust J Gen Pract. 2022 Aug;51(8):586-592. doi: 10.31128/AJGP-04-21-5936. PMID: 35908759.
Nacasch N, Avni C, Toren P. Medical cannabis for treatment-resistant combat PTSD. Front Psychiatry. 2023 Jan 19;13:1014630. doi: 10.3389/fpsyt.2022.1014630. PMID: 36741572; PMCID: PMC9893003.
Rehman Y, Saini A, Huang S, Sood E, Gill R, Yanikomeroglu S. Cannabis in the management of PTSD: a systematic review. AIMS Neurosci. 2021 May 13;8(3):414-434. doi: 10.3934/Neuroscience.2021022. PMID: 34183989; PMCID: PMC8222769.
Clinical Benefit in Depression
García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders. Biomolecules. 2020 Nov 19;10(11):1575. doi: 10.3390/biom10111575. PMID: 33228239; PMCID: PMC7699613.
6.5 Neurological Disorders: Epilepsy, Alzheimer’s, Parkinson’s Disease, and Multiple Sclerosis
6.5.1 Clinical Context
While medical cannabis has been used widely in many other countries, one of the early initiatives for U.S. legalization has been for pediatric epilepsy. This has eventually led to the first cannabis-derived FDA approved medication for epilepsy in 2018.
For other neurologic conditions, many patient support groups and advocates seek to educate themselves, engage in medical cannabis conferences, and encourage further research for conditions like multiple sclerosis, Parkinson’s Disease, and Alzheimers.
Clinical Insight 1: Epilepsy: Prioritize CBD isolates or purified formulations to avoid seizure threshold lowering by THC. MS & PD: Balanced (1:1) THC:CBD products can be used cautiously, with close monitoring for psychoactive side effects or orthostatic
hypotension.
Clinical Insight 2: The CDC reports expected continued rise in age-related neurodegenerative diseases like Alzhiemer’s and Parkinson’s Disease (PD). It is essential for providers to be aware of a variety of treatment options and ways to optimize patient outcomes.
Clinical Insight 3: Consider that there is more than one correct way to initiate treatment for patients. One method is initiating low-dose CBD-predominant formulations to alleviate motor symptoms and anxiety, while avoiding potential THC-induced orthostatic hypotension or psychotropic effects.
Clinical Insight 4: For symptomatic Alzheimer’s patients, consider starting with CBD isolates to address agitation and neuroinflammation while minimizing psychoactive side effects. Review the potential for early intervention with cannabinoid medicines, goal- oriented dietary habits, and consistent exercise, targeting neuroprotective pathways that may slow cognitive decline when combined with consistent lifestyle modifications such as cardiovascular health optimization.
Clinical Insight 5: For advanced cases or as an alternative to the methods described above, balanced THC:CBD (1:1) may be used cautiously for simultaneously treating pain or spasticity, with monitoring for bradykinesia exacerbation in neurologic patients.
6.5.2 Key References
Epilepsy
Stasiłowicz-Krzemień A, Nogalska W, Maszewska Z, Maleszka M, Dobroń M, Szary A, Kępa A, Żarowski M, Hojan K, Lukowicz M, Cielecka-Piontek J. The Use of Compounds Derived from Cannabis sativa in the Treatment of Epilepsy, Painful Conditions, and Neuropsychiatric and Neurodegenerative Disorders. Int J Mol Sci. 2024 May 25;25(11):5749. doi: 10.3390/ijms25115749. PMID: 38891938; PMCID: PMC11171823.
Hidding U, Mainka T, Buhmann C. Therapeutic use of medical Cannabis in neurological diseases: a clinical update. J Neural Transm (Vienna). 2024 Feb;131(2):117-126. doi: 10.1007/s00702-023-02719-1. Epub 2023 Nov 28. PMID: 38015317; PMCID: PMC10791790.
Tzadok M, Gur-Pollack R, Florh H, Michaeli Y, Gilboa T, Lezinger M, Heyman E, Chernuha V, Gudis I, Nissenkorn A, Lerman-Sagie T, Ben Zeev B, Uliel-Sibony S. Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study. Pediatr Neurol. 2024 Jan;150:91-96. doi: 10.1016/j.pediatrneurol.2023.10.012. Epub 2023 Oct 20. PMID: 37995414.
Alzheimer’s | Autism | ADHD
Dallabrida KG, de Oliveira Bender JM, Chade ES, Rodrigues N, Sampaio TB. Endocannabinoid System Changes throughout Life: Implications and Therapeutic Potential for Autism, ADHD, and Alzheimer’s Disease. Brain Sci. 2024 Jun 10;14(6):592. doi: 10.3390/brainsci14060592. PMID: 38928592; PMCID: PMC11202267.
Palmieri B, Vadalà M. Oral THC: CBD cannabis extract in main symptoms of Alzheimer disease: agitation and weight loss. Clin Ter. 2023 Jan-Feb;174(1):53- 60. doi: 10.7417/CT.2023.5009. PMID: 36655645.
Trojan V, Landa L, Šulcová A, Slíva J, Hřib R. The Main Therapeutic Applications of Cannabidiol (CBD) and Its Potential Effects on Aging with Respect to Alzheimer’s Disease. Biomolecules. 2023 Sep 26;13(10):1446. doi: 10.3390/biom13101446. PMID: 37892128; PMCID: PMC10604144.
Ferreira PCL, Bellaver B, Povala G, Brum WS, Tissot C, Badji A, Sloan ME, Benedet AL, Rosa-Neto P, Ashton NJ, Pascoal TA, Leuzy A, Zimmer ER. Endocannabinoid System Biomarkers in Alzheimer’s Disease. Cannabis Cannabinoid Res. 2023 Feb;8(1):77-91. doi: 10.1089/can.2022.0151. Epub 2022 Nov 17. PMID: 36394442; PMCID: PMC10081722.
Siani-Rose M, Cox S, Goldstein B, Abrams D, Taylor M, Kurek I. Cannabis- Responsive Biomarkers: A Pharmacometabolomics-Based Application to Evaluate the Impact of Medical Cannabis Treatment on Children with Autism Spectrum Disorder. Cannabis Cannabinoid Res. 2023 Feb;8(1):126-137. doi: 10.1089/can.2021.0129. Epub 2021 Dec 6. PMID: 34874191; PMCID: PMC9940806.
Parkinson’s Disease
Sousa A, DiFrancisco-Donoghue J. Cannabidiol and Tetrahydrocannabinol Use in Parkinson’s Disease: An Observational Pilot Study. Cureus. 2023 Jul 24;15(7):e42391. doi: 10.7759/cureus.42391. PMID: 37621812; PMCID: PMC10446505.
de Brito Siqueira ALG, Cremasco PVV, Bahú JO, Pioli da Silva A, Melo de Andrade LR, González PGA, Crivellin S, Cárdenas Concha VO, Krambeck K,LodiL, Severino P, Souto EB. Phytocannabinoids:Pharmacologicaleffects, biomedical applications, and worldwide prospection. J Tradit Complement Med. 2023 Aug 26;13(6):575-587. doi: 10.1016/j.jtcme.2023.08.006. PMID: 38020546; PMCID: PMC10658372.
Multiple Sclerosis |
Rainka MM, Aladeen TS, Mattle AG, Lewandowski E, Vanini D, McCormack K, Mechtler L. Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population. Int J MS Care. 2023 May- Jun;25(3):111-117. doi: 10.7224/1537-2073.2022-006. Epub 2022 Dec 12. PMID: 37250194; PMCID: PMC10211357.
Murphy M, Kaur V, Bui HL, Yang T, Erridge S, Holvey C, Coomber R, Rucker JJ, Weatherall MW, Sodergren MH. Clinical outcome analysis of patients with multiple sclerosis - Analysis from the UK Medical Cannabis Registry. Mult Scler Relat Disord. 2024 Jul;87:105665. doi: 10.1016/j.msard.2024.105665. Epub 2024 May 6. PMID: 38728958.
6.6 Immune Modulation in Autoimmune Diseases
6.6.1 Clinical Context
The endocannabinoid system (ECS) modulates immune responses, particularly via CB2 receptors on immune cells. This immunoregulatory effect positions cannabinoids as promising adjuncts for autoimmune conditions.
6.6.2 Key References
Rheumatoid Arthritis (RA) | Psoriatic Arthritis (PA)
Purohit R, Mathai R, Camargo Macias K, Chalise S, Jehu T, Bhaskar N, Bhanusali N. Patient-Reported Outcomes of Pain, Stiffness, and Fatigue Reduction in Rheumatoid and Psoriatic Arthritis With Cannabinoid Use. Cureus. 2024 Oct 25;16(10):e72366. doi: 10.7759/cureus.72366. PMID: 39583459; PMCID: PMC11585972.
Paland N, Hamza H, Pechkovsky A, Aswad M, Shagidov D, Louria-Hayon I. Cannabis and Rheumatoid Arthritis: A Scoping Review Evaluating the Benefits, Risks, and Future Research Directions. Rambam Maimonides Med J. 2023 Oct 29;14(4):e0022. doi: 10.5041/RMMJ.10509. PMID: 37917863; PMCID: PMC10619990.
Inflammatory Bowel Diseases (e.g., Crohn’s):
Nso N, Nyabera A, Nassar M, Alshamam MS, Sumbly V, Vest M, Patel N, Ojong
G, Rizzo V. Cannabis and Its Potential Protective Role Against Inflammatory Bowel Disease: A Scoping Review. Cureus. 2021 Oct 17;13(10):e18841. doi: 10.7759/cureus.18841. PMID: 34804696; PMCID: PMC8597664.
Picardo S, Kaplan GG, Sharkey KA, Seow CH. Insights into the role of cannabis in the management of inflammatory bowel disease. Therap Adv Gastroenterol. 2019 Sep 3;12:1756284819870977. doi: 10.1177/1756284819870977. PMID: 31523278; PMCID: PMC6727090.
Other autoimmune diseases | anti-oxidant | anti-cancer activity
Bukowska B. Current and Potential Use of Biologically Active Compounds Derived from Cannabis sativa L. in the Treatment of Selected Diseases. Int J Mol Sci. 2024 Nov 27;25(23):12738. doi: 10.3390/ijms252312738. PMID: 39684447; PMCID: PMC11641728.
6.7 Summary for Physicians
Introduction
The ECS is extensive in human anatomy and physiology. This anatomic layout provides for targeting a wide variety of medical conditions. Additionally, there are multiple formulations and routes of administration, increasing personalization for medical cannabis patient care.
Chronic Pain and Spasticity
Evidence robustly supports cannabinoid efficacy, especially for neuropathic pain and MS-related spasticity.
Start with low-dose THC:CBD formulations, titrate as needed.
Opioid Crisis
Integrate cannabis as an opioid-sparing agent, supported by epidemiological studies showing reduced opioid prescriptions and overdose mortality in states with medical cannabis programs.
Mental Health
Anxiety & PTSD: Favor CBD-dominant products, add low-dose THC for refractory PTSD if tolerated.
Depression: Emerging data; consider adjunctive use with conventional antidepressants.
Neurological Disorders
Epilepsy: Utilize FDA-approved CBD products (Epidiolex).
Alzheimer’s, Autism, ADHD: has potential to provide relief for these conditions. In several studies symptomatic improvement is reported.
PD & MS: In some studies, balanced THC:CBD can improve pain, spasticity, and sleep; close observation for neuropsychiatric side effects.
Autoimmune and Inflammatory Diseases
CBD-Rich therapies modulate inflammatory pathways, beneficial in RA, Crohn’s, and potentially SLE.
Monitor response using objective measures (CRP, ESR) and patient-reported outcomes.
Key Takeaways
Cannabinoid conversations and recommendations can be supported by clinical and mechanistic research. This can assist you in offering a multifaceted approach to managing chronic pain, spasticity, mental health conditions, neurological disorders and autoimmune diseases. As the body of evidence expands, harness cannabis’s opioid-sparing potential and immunomodulatory benefits while tailoring THC:CBD ratios to patient-specific needs. Combine your expanding knowledge with consistent patient follow-up, proper dosing regimens, and awareness of evolving guidelines ensure safe, effective, and evidence-based therapeutic outcomes.