Medical Cannabis: Difference between revisions

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== Definition/Description: ==
== Introduction  ==
[[File:Cannabis oil.jpeg|right|frameless]]
Cannabis sativa (C. sativa) is a flowering, fast growing shrub, commonly known as hemp, cannabis, or marijuana. It originates from Central Asia, and is widely distributed in temperate and tropical areas. For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes.<ref>Maule WJ. Medical uses of marijuana (Cannabis sativa): fact or fallacy?. British journal of biomedical science. 2015 Jan 1;72(2):85-91.</ref> Phytocannabinoids are a family of compounds that are found in some flowering plants (such as cannabis plant), which is known for its psychotogenic and euphoric effects;<ref>Gülck T, Møller BL. Phytocannabinoids: origins and biosynthesis. Trends in Plant Science. 2020 Jul 6.</ref> the main psychotropic constituent of cannabis is Tetrahydrocannabinol (THC).<ref name=":2">PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 16078, Dronabinol; [cited 2022 Jan. 29]. Available from: <nowiki>https://pubchem.ncbi.nlm.nih.gov/compound/Dronabinol</nowiki></ref> THC is one of the at least 113 recognized cannabinoids in C. sativa. The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body<ref>Breijyeh,Z.;Jubeh,B.Bufo, S.A.; Karaman, R.; Scrano, L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses.Toxins 2021, 13, 117. Available from: <nowiki>https://res.mdpi.com/d_attachment/toxins/toxins-13-00117/article_deploy/toxins-13-00117.pdf</nowiki>


As a result of cannabis decriminalization and legalization throughout the world, healthcare professionals are faced with more questions from patients regarding cannabis and its use. Healthcare professionals have a responsibility to provide evidence-based guidance on this important medical and social issue. Cannabis has significant health benefits and therapeutic applications to a vast array of medical conditions explored in this page. As with any medical substance, cannabis use also presents with associated risks. This page describes the many uses of cannabis in relation to specific patient populations. The purpose of this page is to provide a comprehensive, up-to-date educational resource for healthcare professionals, patients, and caregivers guided by current evidence-based research. Additionally, the information presented will attempt to dispel many myths and help clear the smoke around issues surrounding the cannabis plant. This page will be updated continually in the future. This page is dedicated to past and future patients.<br>  
(accessed 5.4.2021)
</ref>.
* Many people around the world believe that the drug should be readily available for both medical and recreational use; however governments around the world still have strict laws about its usage.
* Each country has its own laws and regulations surrounding the drug; some places are more relaxed, whist others still believe the drug should be an illegal substance<ref>best in Au [https://bestinau.com.au/marijuana-laws-from-around-the-world-where-is-cannabis-legal/ Where is cannabis legal] Available from:https://bestinau.com.au/marijuana-laws-from-around-the-world-where-is-cannabis-legal/ (accessed 5.4.2021)</ref>.
Cannabidiol (CBD), the major non-psychoactive constituent of ''Cannabis sativa'' L., has gained popularity as a potential treatment for certain conditions<ref name=":3">Argueta DA, Ventura CM, Kiven S, Sagi V, Gupta K. A balanced approach for cannabidiol use in chronic pain. Frontiers in pharmacology. 2020 Apr 30;11:561.</ref> See below).
== Types of medicinal cannabis products ==
[[File:Cannabis pills.jpeg|right|frameless|400x400px]]
Cannabis is a complex plant comprising more than 500 constituents, including approximately 100 cannabinoids. The main active ingredients used for medical purposes are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive part of cannabis that produces a ‘high’, and has been used to treat symptoms such as nausea, pain and muscle spasticity. CBD has no psychoactive properties, and has been used to treat several inflammatory disorders and epilepsy.<ref name=":3" />


Cannabis is classified as a member of the cannabaceae plant family. Cannabis is classified under the single species of hemp (C. sativa). The female version of hemp is considered “marijuana” and consists of the indica, sativa, and ruderalis varieties. Cannabis has thousands of varieties and the effects of each variety are different. Hops belongs to the cannabaceae plant family as well. Hops is used in the production of beer, a celebrated legal drug. <br><ref>Classification | USDA PLANTS [Internet]. Classification | USDA PLANTS. [cited 2016Apr13]. Retrieved from: http://plants.usda.gov/java/classificationservlet?source=display</ref><ref>The Editors of Encyclopædia Britannica. cannabis [Internet]. Encyclopedia Britannica Online. Encyclopedia Britannica; [cited 2016Apr13]. Retrieved from: http://www.britannica.com/plant/cannabis-plant</ref><br>  
Medicinal cannabis products can come in three main forms:
# Pharmaceutical: Natural and synthetic medical-grade products with standardized content. The three main products are:
#* Dronabinol: Synthetic form of THC<ref name=":2" />
#* Nabilone: Synthetic form of THC
#* Nabiximols: Chemically pure 50:50 mixture of TCH and CBD.
# Medicinal-grade herbal cannabis: Produced and processed in controlled standard conditions to a medical grade, free of adulterants, higher levels of CBD and other cannabinoids, and contains lower levels of THC. This is provided in herbal form, or processed as an oil, balm, capsule or pill.
# Herbal cannabis on the illegal market: Potentially unstable THC and CBD, and may contain adulterants.<ref name=":0">RACGP [https://www.racgp.org.au/advocacy/position-statements/view-all-position-statements/clinical-and-practice-management/medical-cannabis Medicinal Cannabis] Available from:https://www.racgp.org.au/advocacy/position-statements/view-all-position-statements/clinical-and-practice-management/medical-cannabis (accessed 5.4.2021)</ref>  


== Marijuana and Related Cannabinoids <br> ==
== The Evidence ==
[[File:Evidence.jpeg|right|frameless]]
At present, the evidence base for the use of medicinal cannabis products is limited.<ref>O’Brien K. Medicinal cannabis: Issues of evidence. European Journal of Integrative Medicine. 2019 Jun 1;28:114-20.</ref> The current evidence base for the use of medicinal cannabis products is heterogeneous, comprising a small number of randomized clinical trials when stratified by condition, symptom or intervention type.<ref>Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV. Cannabinoids for medical use. JAMA [Internet]. 2015; 313 (24): 2456.</ref> <ref name=":0" />These studies are of variable quality, including those with high risk of bias (eg incomplete outcome data), low statistical power, and short follow-up time.
* Recent reviews and analyses indicate there may be some therapeutic benefits of medicinal cannabis products in certain conditions but further research on the treatment efficacy and longer term side effects are warranted.
* Currently, most research and evidence on medicinal cannabis products have come from five clinical conditions: [[Multiple Sclerosis (MS)|multiple sclerosis]]; [[Palliative Care Competence Framework for Physiotherapists|palliative care]]; [[epilepsy]]; nausea and vomiting; and [[Chronic Pain|chronic non-cancer pain]].<ref name=":0" />
* As there is limited scientific evidence to support the use of medicinal cannabis in most conditions, and in many cases the evidence is for its use together with other medicines, it should be used only when approved treatments have been tried and have failed to manage conditions and symptoms.<ref name=":1">Aust Government [https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-australia-patient-information Guidance on medicinal cannabis] Available from:https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-australia-patient-information (accessed 5.4.2021)</ref>


There are two main chemical cannabinoids that have been extensively studied for their effects on the different body systems. These two substances are Tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is the chemical responsible for the psychotropic effects associated with smoking or ingesting marijuana. CBD on the other hand, does not have psychoactive properties and may balance or inhibit the psychotropic effects of THC. CBD may be more important than THC in producing therapeutic effects such as analgesia, decreased inflammation, decreased spasticity, and antiseizure effects. <ref name="1">Ciccone CD. Medical Marijuana: Just the Beginning of a Long, Strange Trip? Physical Therapy. 2016;97(2):239–48.</ref><br>
=== Chronic Pain ===
The International Association for the Study of Pain (IASP) taskforce looked at all the available research published in peer-reviewed journals on the use of medicinal cannabis for pain management, from preclinical studies to human trials.


== Federal Classification<br> ==
They concluded overall the studies’ “quality, rigour, and transparency of reporting” of benefits and harms needs to be improved across the board. The IASP taskforce demands higher quality data, for example through randomized controlled trials, to determine the safety and efficacy of using medicinal cannabis for pain<ref>IASP Position Statement on the Use of Cannabinoids to Treat Pain Available from:https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=11145&navItemNumber=643 (accessed 5.4.2021)
</ref>


1970 - The Federal classification of cannabis legally: Schedule 1 narcotic, no accepted medical value.<br>  
=== Multiple sclerosis ===
Anout 50% of the studies in a recent systematic reviews showed that medicinal cannabis products may be effective for pain, spasticity, sleep and bladder function. The other half had inconclusive results.<ref name=":0" />


As defined by the United States Controlled Substance Act (CSA).  
=== Epilepsy ===
A number of studies have found low evidence for the use of medicinal cannabis products for the treatment of paediatric epilepsy, and for patients up to aged 25 years, especially when first-line treatments (ie anti-epileptic drugs) have been found to be ineffective. The numbers needed to treat are as follows:
* 50% or greater reduction in seizure frequency: 8
* Complete seizure freedom: 17
* Improvement in parental-reported [[Quality of Life|quality of life]]: 5
* The numbers needed to harm for any adverse event was 3, and serious adverse event was 23.


“Schedule I drugs are defined as:  
=== Palliative care ===
The use of medicinal cannabis products in palliative care is currently unclear.
[[File:Pain stress brain.png|right|frameless]]


(A) The drug or other substance has a high potential for abuse.  
=== Nausea and vomiting ===
A small number of studies have found relief of nausea and vomiting in patients with [[Oncology|cancer]] who are undergoing [[Chemotherapy Side Effects and Syndromes|chemotherapy]]; however, the evidence is lacking and some were compared with now out-of-date practices.


(B) The drug or other substance has no currently accepted medical use in treatment in the United States.  
=== Chronic non-cancer pain ===
There is some evidence available for the treatment of [[Neuropathic Pain|neuropathic pain]] using medicinal cannabis products; however, the magnitude of effect is small. One systematic review found that the numbers needed to treat was 22 for a 30% reduction and 26 for a 50% reduction in self-reported pain intensity<ref name=":0" />
== Side Effects ==
Like all prescription medicines, medicinal cannabis products can have side effects. The extent of effects of these can vary with the type of medicinal cannabis product and between individuals.
* In general, the side effects of CBD-rich products are less than those for high-THC products, but because the required doses for CBD can be quite high in conditions such as pediatric epilepsies, a proportion of patients encounter side-effects with these CBD doses.
* The known side-effects from medicinal cannabis treatment (both CBD and THC) include fatigue and sedation, vertigo, nausea and vomiting, fever, decreased or increased appetite, dry mouth, and diarrhea.
* THC (and products high in THC) have been associated with convulsions, feeling high or feeling dissatisfied, [[depression]], confusion, hallucinations, paranoid delusions, psychosis, and cognitive distortion (having thoughts that are not true)<ref name=":1" />.


(C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.”<br><ref>Controlled Substance Schedules [Internet]. Resources -. [cited 2016Apr10]. Retrieved from: http://www.deadiversion.usdoj.gov/schedules/</ref><br>
== Relevance to Physical Therapy ==
Physiotherapists should be able to educate patients on the reported benefits of cannabis (eg chronic pain, MS, spasticity, and chemotherapy-induced nausea and vomiting) as well as potential adverse effects. Also, trends in the medical use of cannabis can be studied in relation to the extant laws of the country of practice to understand what is allowed in a region concerning the use of medicinal cannabis.


Until recently, this classification had removed marijuana as a medicinal agent and severely restricted any research into its potential clinical benefits. For example, it is difficult to perform well-controlled clinical trials on a substance when the government has determined that the substance has no clinical applications. <ref name="1" /><br>
== Summary of Evidence by Condition ==
{| class="wikitable"
!Condition
!Products
!Current evidence quality
|-
! colspan="3" |Multiple sclerosis
|-
|Pain
|Dronabinol, THC extracts
|Low to high and inconsistent
|-
|Disability and its progression
|
|None
|-
|Spasticity
|Nabiximols and THC:CBD
|Low and inconsistent
|-
|Bladder function
|
|None
|-
|Ataxia and tremor
|
|None
|-
|Sleep
|
|None
|-
|Quality of life
|Nabiximols and THC:CBD
|Low and inconsistent
|-
! colspan="3" |Epilepsy
|-
| rowspan="4" |To reduce and/or eliminate the number of seizures
|CBD when used in conjunction with anti-epileptic drugs
|Low to very low
|-
|Oral cannabis extracts (OCEs)
|Very low
|-
|CBD:THC
|Very low
|-
|Cannabis sativa
|Very low
|-
| rowspan="5" |Quality of life
|CBD
|Low
|-
|Oral cannabis extracts (OCEs)
|Very low
|-
|CBD:THC
|Very low
|-
|Cannabis sativa
|Very low
|-
|THC
|Very low
|-
! colspan="3" |Palliative care
|-
|Alzheimer's disease
|Dronabinol
|Unclear
|-
| rowspan="3" |Advanced cancer symptom control
|Dronabinol, THC:CBD, THC
|Unclear but some evidence against use
|-
|Cannabis sativa
|Unclear
|-
|Nabilone
|Unclear
|-
! colspan="3" |Nausea and vomiting
|-
| rowspan="7" |
|Dronabinol
|Low to moderate
|-
|Nabilone
|Very low to moderate
|-
|THC
|Low, insufficient evidence
|-
|Levonantradol
|Low to moderate
|-
|THC:CBD
|Insufficient evidence
|-
|Cannabis sativa extract
|Unclear
|-
|Naximols
|Insufficient evidence
|-
! colspan="3" |Chronic non-cancer pain
|-
| rowspan="7" |
|Nabiximols
|Moderate to high
|-
|Dronabinol
|Low to moderate
|-
|Nabilone
|Very low
|-
|Cannabis sativa
|Very low
|-
|THC extract
|Moderate
|-
|THC:CBD extract
|Low to moderate
|-
|Ajulemic acid
|Very low
|}
Nabiximols is a TGA-registered medicine, under the tradename Sativex. It is a standardised extract of cannabis, containing roughly equal amounts of THC and CBD.


However, now that more and more states are starting to leglaize the use of medical and recreational marijuana, better studies may soon start to arise in the literature. <br>
Dronabinol is a synthetic form of THC.


== State Classifications <br>  ==
Nabilone is a cannabinoid synthesised in the laboratory, and has actions similar to THC although its chemical structure is different.


As of June, 2016, 28 states plus District of Columbia, Guam, and Puerto Rico now allow for comprehensive public medical marijuana and cannabis programs.
Ajulemic acid is a cannabinoid synthesised in the laboratory. It is similar to a breakdown product (metabolite) of THC but does not have psychoactive properties.<ref name=":1" />
<div>
California - Became the first state to legalize cannabis for medical use in 1996.
 
Colorado and Washington - November, 2012 they became the first two states to legalize recreational use of marijuana for individuals over the age of 21 (Colorado Amendment 64 and Washington Initiative 502).
 
Oregon - June, 2010 Oregon Board of Pharmacy reclassified marijuana from a Schedule I drug to a Schedule II drug. Oregon is the first state in the nation to make marijuana anything less than a Schedule I drug.&nbsp; <ref name="2">http://arcweb.sos.state.or.us/pages/rules/oars_800/oar_855/855_080.html</ref><br><br>
</div>
 
== Patient Demongraphics and Self Reported Usage <br>  ==
 
Information for the following tables was gathered from a sample of 1,746 patients of nine medical marijuana evaluation clinics in California. These table may provide insight about potential patients based on demographics and conditions.
 
[[Image:Table 1 pt demographics .jpg|394x509px]][[Image:Table 2 Self Reported Benefits .jpg|389x522px]]<br>
 
[[Image:Table 3 Conditions treated .jpg|390x390px]]&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Image:Table 4 other treatment modalities .jpg|382x355px]] <br>From: Copyright © Taylor &amp; Francis Group, LLCISSN: 0279-1072 print/2159-9777 online DOI: 10.1080/02791072.2011.587700 <br>
 
== Health Effects of Cannabis and Cannabinoids <br>  ==
 
This section of the page will be continuously updated.  
 
The National Academies of Science, Engineering, and Medicine worked together to create a comprehensive report for the current state of evidence regarding what is known about the health effects of cannabis and cannabis derived products. Below are the conclusions of these findings.
 
The committee developed standard language to categorize the weight of the evidence regarding whether cannabis or cannabinoids used for therapeutic purposes are an effective or ineffective treatment for certain prioritized health conditions, or whether cannabis or cannabinoids used primarily for recreational purposes are statistically associated with certain prioritized health conditions. The conclusions from this research are organized by level of evidence:<br>
 
*<u>Conclusive Evidence</u>: strong evidence from RCTs to support or refute the conclusion. Firm conclusions can be made and the limitations to the evidence, including chance, bias, and/or confounding factors can be ruled out with reasonable confidence.
*<u>Substantial Evidence</u>: At this level, there are several supportive findings from good-quality studies with very few or no credible opposing findings. Firm conclusion can be made, but minor limitations, can’t be ruled out with reasonable confidence.
*<u>Moderate Evidence</u>: There are several findings from good to fair quality studies with very few or no credible opposing findings. General conclusions can be made but not without having a general limitation.
*<u>Limited Evidence</u>: There are supportive findings from fair-quality studies or mixed findings with most favoring one conclusion. Conclusions can be made but with significant uncertainty due to various limitations.
*<u>No or Insufficient Evidence</u>: There are mixed findings, a single poor study, or this factor hasn't been studied at all. No conclusion can be made because of substantial uncertainty due to various limitations or lack of evidence. <br>
 
<br>
 
'''<u>Conclusions for: Therapeutic Effects</u>''' (https://www.nap.edu/read/24625/chapter/6)<br>
 
<u>Conclusive or Substantial Evidence for effectiveness:</u>
 
*Treatment of chronic pain in adults.
*Antiemetics in the treatment of chemotherapy-induced nausea and vomiting.
*Improving patient-reported multiple sclerosis (MS) spasticity symptoms.
 
<u>Moderate Evidence for effectiveness:</u>
 
*Improving short term sleep outcomes in individuals with sleep disturbances associated with obstructive sleep apnea, fibromyalgia, chronic pain, and multiple sclerosis.
 
<u>Limited Evidence for effectiveness:</u>
 
*Increasing appetite and decreasing weight loss associated with HIV/AIDS
*Improving clinician-measured MS spasticity symptoms
*Improving symptoms of Tourette’s Syndrome
*Improving anxiety symptoms, as assessed by a public speaking test, in individuals with social anxiety disorders.
*Improving symptoms of PTSD
 
<u>Limited Evidence of a statistical correlation between cannabinoids and:</u>
 
*Better outcomes (mortality and disability) after a TBI or intracranial hemorrhage.
 
<u>Limited Evidence for ineffectiveness of:</u>
 
*Improving symptoms associated with dementia
*Improving intraocular pressure associated with glaucoma
*Reducing depressive symptoms in individuals with chronic pain or MS
 
<u>Insufficient Evidence to support or refute the conclusion for effective treatment for:</u>
 
*Cancers, including glioma.
*Cancer-associated anorexia cachexia syndrome and anorexia nervosa.
*Symptoms of IBS
*Epilepsy
*Spasticity in patients with paralysis due to SCI
*Symptoms associated with amyotrophic lateral sclerosis.
*Chorea and certain neuropsychiatric symptoms with Huntington’s Disease.
*Motor system symptoms associated with Parkinson’s disease or the levodopa-induced dyskinesia.
*Dystonia
*Achieving abstinence inthe abuse of addictive substances
*Mental health outcomes in individuals with schizophrenia or schizophreniform psychosis.
 
<br>
 
<u>'''Conclusions for: Cancer'''</u> (https://www.nap.edu/read/24625/chapter/7 )<br>
 
<u>Moderate Evidence of no statistical association between cannabis use and:</u><br>
 
*Incidence of lung cancer or head and neck cancers
 
<u>Limited Evidence of a statistical association between cannabis smoking and:</u><br>
 
*Non-seminoma-type testicular germ cell tumors
 
<u>No or Insufficient Evidence to support or refute any association between cannabis and:</u><br>
 
*Incidence of esophageal cancer
*Incidence of prostate cancer, cervical cancer, malignant gliomas, non-Hodgkin lymphoma, pencils cancer, anal cancer, Kaposi’s sarcoma, or bladder cancer.
*Subsequent risk of developing acute myeloid leukemia/acute non-lymphoblastic leukemia, acute lymphoblastic leukemia, rhahbomyosarcoma, astrocytoma, or neuroblastoma in offspring. <br>
 
<br><u>'''Conclusions for: Cardiometabolic Risk'''</u> (https://www.nap.edu/read/24625/chapter/8 )<u></u><br>
 
<u>Limited Evidence of a statistical correlation between cannabis use and</u>:<br>
 
*Triggering of acute myocardial infarction
*Ischemic stroke and subarachnoid hemorrhage
*Decreased risk of metabolic syndrome and diabetes Increased risk of prediabetes.
 
<u>No Evidence to support or refute a statistical correlation between chronic effects of cannabis use and:</u><br>
 
*Increased risk of acute myocardial infarction.
 
<u>'''<br>'''</u>
 
<u>'''Conclusions for: Respiratory Disease'''</u> (https://www.nap.edu/read/24625/chapter/9 )<u></u><br>
 
<u>Substantial Evidence of a statistical association between cannabis smoking and:</u><br>
 
*Worse respiratory symptoms and more frequent chronic bronchitis episodes (long-term cannabis smoking)
 
<u>Moderate evidence of a statistical association between cannabis smoking and:</u><br>
 
*Improved airway dynamics with acute use, but not with chronic use.
*Higher forced vital capacity (FVC)
 
<u>Moderate Evidence of a statistical association between the cessation of cannabis smoking and:</u><br>
 
*Improvements in respiratory symptoms.
 
<u>Limited Evidence of a statistical association between cannabis smoking and:</u><br>
 
*An increased risk of developing COPD when controlled for tobaccos use (occasional cannabis smoking).
 
<u>No or Insufficient Evidence to support or refute a statistical association:</u><br>
 
*Hospital admissions for COPD
*Asthma development or asthma exacerbations<br><br>
 
<u>'''Conclusions for: Immunity'''</u> (https://www.nap.edu/read/24625/chapter/10 )
 
<u>There is limited evidence of a statistical association between cannabis smoking and:</u>
 
*A decrease in the production of several in ammatory cytokines in healthy individuals<u></u>
 
<u>There is limited evidence of no statistical association between cannabis use and:</u>
 
*The progression of liver brosis or hepatic disease in individuals with viral Hepatitis C (HCV) (daily cannabis use)<u></u>
 
<u>There is no or insufficient evidence to support or refute a statistical association between cannabis use and:</u>
 
*Other adverse immune cell responses in healthy individuals (cannabis smoking)
*Adverse effects on immune status in individuals with HIV (cannabis or dronabinol use)
 
Increased incidence of oral human papilloma virus (HPV) (regular cannabis use).<br>
 
<br>
 
<u>'''Conclusions for: Injury and Death'''</u> (https://www.nap.edu/read/24625/chapter/11 )<u></u><br>
 
<u>There is substantial evidence of a statistical association between cannabis use and:</u><br>
 
*Increased risk of motor vehicle crashes<br>
 
<u>There is moderate evidence of a statistical association between cannabis use and:</u><br>
 
*Increased risk of overdose injuries, including respiratory distress, among pediatric populations in U.S. states where cannabis is legal<br>
 
<u>There is no or insufficient evidence to support or refute a statistical association between cannabis use and:</u><br>
 
*All-cause mortality (self-reported cannabis use)
*Occupational accidents or injuries (general, non-medical cannabis use)
*Death due to cannabis overdose
 
<br>
 
<u>'''Conclusions for: Prenatal, Perinatal, and Neonatal Exposure'''</u> (https://www.nap.edu/read/24625/chapter/12 )<u></u><br>
 
<u>There is substantial evidence of a statistical association between maternal cannabis smoking and:</u><br>
 
*Lower birth weight of the offspring
 
<u>There is limited evidence of a statistical association between maternal cannabis smoking and:</u><br>
 
*Pregnancy complications for the mother
*Admission of the infant to the neonatal intensive care unit (NICU)<br>
 
<u>There is insufficient evidence to support or refute a statistical association between maternal cannabis smoking and:</u><br>
 
*Later outcomes in the offspring (e.g., sudden infant death syndrome, cognition/academic achievement, and later substance use)
 
<br>
 
<u>'''Conclusions for: Psychosocial'''</u> (https://www.nap.edu/read/24625/chapter/13 )
 
<u>There is moderate evidence of a statistical association between cannabis use and:</u><br>
 
The impairment in the cognitive domains of learning, memory, and attention (acute cannabis use)<br>
 
<u>There is limited evidence of a statistical association between cannabis use and:</u><br>
 
*Impaired academic achievement and education outcomes.
*Increased rates of unemployment and/or low income.
*Impaired social functioning or engagement in developmentally appropriate social roles.
 
<u>There is limited evidence of a statistical association between sustained abstinence from cannabis use and:</u><br>
 
*Impairments in the cognitive domains of learning, memory, and attention <br><br>
 
<u>'''Conclusions for: Mental Health'''</u> (https://www.nap.edu/read/24625/chapter/14 )<u></u>
 
<u>There is substantial evidence of a statistical association between cannabis use and:</u>
 
*The development of schizophrenia or other psychoses, with the highest risk among the most frequent users
 
<u>There is moderate evidence of a statistical association between cannabis use and:</u><br>
 
*Better cognitive performance among individuals with psychotic disorders and a history of cannabis use
*Increased symptoms of mania and hypomania in individuals diagnosed with bipolar disorders (regular cannabis use).
*A small increased risk for the development of depressive disorders
*Increased incidence of suicidal ideation and suicide attempts with a higher incidence among heavier users
*Increased incidence of suicide completion.
*Increased incidence of social anxiety disorder (regular cannabis use)
 
<u>There is moderate evidence of no statistical association between cannabis use and:</u>
 
*Worsening of negative symptoms of schizophrenia (e.g., blunted affect) among individuals with psychotic disorders.<br>
 
<u>There is limited evidence of a statistical association between cannabis use and:</u>
 
*<u></u>An increase in positive symptoms of schizophrenia (e.g., hallucinations) among individuals with psychotic disorders.
*The likelihood of developing bipolar disorder, particularly among regular or daily users.
*The development of any type of anxiety disorder, except social anxiety disorder.
*Increased symptoms of anxiety (near daily cannabis use)
*Increased severity of posttraumatic stress disorder symptoms among individuals with posttraumatic stress disorder.
 
<u>There is no evidence to support or refute a statistical association between cannabis use and:</u>
 
*<u></u>Changes in the course or symptoms of depressive disorders
*The development of posttraumatic stress disorder.
 
<br>
 
<u>'''Conclusions for: Problem Cannabis Use'''</u> (https://www.nap.edu/read/24625/chapter/15 )<u></u>
 
<u>There is substantial evidence that:</u><br>
 
*Stimulant treatment of attention deficit hyperactivity disorder (ADHD) during adolescence is not a risk factor for the development of problem cannabis use.
*Being male and smoking cigarettes are risk factors for the progression of cannabis use to problem cannabis use.
*Initiating cannabis use at an earlier age is a risk factor for the development of problem cannabis use.
 
<u>There is substantial evidence of a statistical association between:</u><br>
 
*Increases in cannabis use frequency and the progression to developing problem cannabis use.
*Being male and the severity of problem cannabis use, but the recurrence of problem cannabis use does not differ between males and females.
 
<u>There is moderate evidence that:</u>
 
*Anxiety, personality disorders, and bipolar disorders are not risk factors for the development of problem cannabis use
*Major depressive disorder is a risk factor for the development of problem cannabis use.
*Adolescent ADHD is not a risk factor for the development of problem cannabis use.
*Being male is a risk factor for the development of problem cannabis use.
*Exposure to the combined use of abused drugs is a risk factor for the development of problem cannabis use.
*Neither alcohol nor nicotine dependence alone are risk factors for the progression from cannabis use to problem cannabis use
*During adolescence the frequency of cannabis use, oppositional behaviors, a younger age of rst alcohol use, nicotine use, parental substance use, poor school performance, antisocial behaviors, and childhood sexual abuse are risk factors for the development of problem cannabis use.
 
<u>There is moderate evidence of a statistical association between:</u><br>
 
*A persistence of problem cannabis use and a history of psychiatric treatment
*Problem cannabis use and increased severity of posttraumatic stress disorder symptoms
 
<u>There is limited evidence that:</u><br>
 
*Childhood anxiety and childhood depression are risk factors for the development of problem cannabis use.
 
<br>
 
<u>'''Conclusions for: Abuse of Other Substances'''</u> (https://www.nap.edu/read/24625/chapter/16 )<br><u>There is moderate evidence of a statistical association between cannabis use and:</u><br>
 
*The development of substance dependence and/or substance abuse disorder for substances including alcohol, tobacco, and other illicit drugs.
 
<u>There is limited evidence of a statistical association between cannabis use and:</u><br>
 
*The initiation of tobacco use.
*Changes in the rates and use patterns of other licit and illicit substances.<br><br>
 
<u>'''Challenges and barriers to this research:'''</u> (https://www.nap.edu/read/24625/chapter/17 )<br>
 
*There are several challenges and barriers in conducting cannabis and cannabinoid research, including:
*There are specific regulatory barriers, including the classification of cannabis as a Schedule I substance, that impede the advancement of cannabis and cannabinoid research.
*It is often difficult for researchers to gain access to the quantity, quality, and type of cannabis product necessary to address specific research questions on the health effects of cannabis use.
*A diverse network of funders is needed to support cannabis and cannabinoid research that explores the bene cial and harmful effects of cannabis use.
*To develop conclusive evidence for the effects of cannabis use for short- and long-term health outcomes, improvements and standardization in research methodology (including those used in controlled trials and observational studies) are needed
 
<br>Reference: National Academies of Science, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. Doi: 10.17226/24625 <br><br>
 
== Drug Interactions  ==
 
A study in JAMA found a “25% reduction in opioid related deaths in states with medical marijuana programs.”<ref>Hayes MJ, Brown MS. Medical Cannabis Laws and Opioid Mortality [Internet]. JAMA Network. [cited 2016Apr13]. Retrieved from: http://archinte.jamanetwork.com/article.aspx?articleid=1898878</ref> The study states, “Medical marijuana laws, when implemented, may represent a promising approach for stemming runaway rates of nonintentional opioid analgesic effects.” As the epidemic negatively impacts the country, politicians like Elizabeth Warren call for more studies to be done on cannabis to curb the destructive effects of the opioid epidemic.<ref>Holpuch A. Elizabeth Warren asks CDC to consider legal marijuana as alternative painkiller [Internet]. The Guardian. Guardian News and Media; 2016 [cited 2016Apr13]. Retrieved from: http://www.theguardian.com/us-news/2016/feb/12/elizabeth-warren-medical-marijuana-painkiller-opioid-abuse</ref><br>
 
Additionally, “there is some evidence of cross-tolerance between cannabinoids and opioids.”<ref name="Cart Before the Horse" />
 
== Relevance to Physical Therapy Rehabilitation <br><br>  ==
 
<br>Since medical and recreational marijuana is becoming legalized in a greater number of states, there is an increased likelihood that physical therapists will treat patients using marijuana to combat different musculoskeletal and neurological conditions. Drug prescription does not fall under the scope of physical therapy practice; therefore, the major role of the therapist is to be an educational resource for patients with questions about the use of medical marijuana. It is recommended that therapists explain the benefits and drawbacks of medical marijuana rather than directly suggesting that the patient initiate using the substance. (Reference 1) <br>
 
Patients may not be well educated on the different routes of administration of marijuana and its extracts. Below is a chart of different marijuana based products with their associated effect times. <br>
 
[[Image:Cannabinoid Administration route .jpg]]
 
Patients who are known users of medicinal or recreational marijuana for analgesic purposes should be encouraged to keep a pain journal.Therapists should have patients periodically complete valid and reliable pain scales to ensure that the treatment is providing the desirable effects. One of the major roles of the physical therapist is to monitor patients for potential abuse of the substance and/or co-administration with alcohol, benzodiazepines, or opioids. These patients may present with amplified confusion or somnolence and demonstrate personality changes or psychotic-like behaviors. If these signs are noted, the problem should be reports the prescribing physician by the therapist. (Reference 1) <br>
 
In the table below are several presecribed cannabinoid based medications that have been either been approved by the FDA or are currently under clinical trials. These drugs may start to be prescribed more in the future. <br>
 
[[Image:Prescription Cannabinoid Products .jpg]]<br>
 
Therapists should also be able to identify patients for Cannabis Use Disorder (CUD). (See diagnostic criteria questionnaire below) Patients using marijuana for the use of chronic pain are less likely to suffer from cannabis use problems compared with individuals who used medical cannabis for other reasons (e.g., anxiety, insomnia, and muscle spasms). (Reference 3) <br>
 
This has been shown to occur primarily in recreational users and risk of this disorder in individuals using medical marijuana has yet to be fully established. (Reference 4) <br>
 
[[Image:Cannabis Use Disorder .jpg]]
 
== Case Reports/ Case Studies:<br>  ==
 
<br>
 
==  ==
 
This page will be continually updated in the future.
 
HIV:<br>Woolridge E, Barton S, Samuel J, Osorio J, Dougherty A, Holdcroft A. Cannabis use in HIV for pain and other medical symptoms. J Pain Symptom Manage 2005;29(4):358-67.<br>http://www.ncbi.nlm.nih.gov/pubmed/15857739
 
Multiple Sclerosis:&nbsp;
 
Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. European Neurology 1997;38:44-48.<br>http://www.ncbi.nlm.nih.gov/pubmed/9252798
 
Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E. Cannabis use in patients with multiple sclerosis. Mult Scler 2006;12(5):646-51.<br>http://www.ncbi.nlm.nih.gov/pubmed/17086912
 
Spinal Cord Injury:
 
Malec J, Harvey RF, Cayner JJ. Cannabis effect on spasticity in spinal cord injury. Archives of Physical Medicine and Rehabilitation 1982;63:116-118.<br>http://www.ncbi.nlm.nih.gov/pubmed/6978699
 
Crohn's Disease: <br>Lal S, Prasad N, Ryan M, Tangri S, Silverberg MS, Gordon A, Steinhart H. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2011;23(10):891-6.<br>http://www.ncbi.nlm.nih.gov/pubmed/21795981<br><br>
 
== Resources <br>  ==
 
For information regarding your states cannabis laws: <br>http://norml.org/
 
For information regarding which strains you or your patient's are using:&nbsp;
 
https://www.leafly.com/
 
For information regarding cannabis therapeutics for different conditions including veterans: <br>http://www.safeaccessnow.org/
 
Realm of Caring: Pediatric Epilepsy
 
https://www.theroc.us/
 
Information on legal issues: Marijuana policy project:
 
https://www.mpp.org/
 
Drug policy information:
 
http://www.drugpolicy.org/
 
<br>
 
== Recent Related Research (from [http://www.ncbi.nlm.nih.gov/pubmed/ Pubmed])  ==
 
see tutorial on [[Adding PubMed Feed|Adding PubMed Feed]]
<div class="researchbox">
<rss>http://www.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=169y_86ceC_-bu0xhVp8W0LNFt6JjWkKQVWt20NBFGwPUebovR|charset=UTF-8|short|max=10</rss>
</div>  
== References  ==
 
see [[Adding References|adding references tutorial]].


==References==
<references />  
<references />  


[[Category:Bellarmine_Student_Project]]
[[Category:Bellarmine_Student_Project]]
[[Category:Global Health]]
[[Category:Pharmacology]]
[[Category:Pain]]

Latest revision as of 17:07, 4 February 2022

 

Original Editors -Mark Wojda from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Ryan Scinta, Lucinda hampton, Elaine Lonnemann, Kim Jackson, Ryan Barry, WikiSysop, Mark Wojda and Joseph Ayotunde Aderonmu   

Introduction[edit | edit source]

Cannabis oil.jpeg

Cannabis sativa (C. sativa) is a flowering, fast growing shrub, commonly known as hemp, cannabis, or marijuana. It originates from Central Asia, and is widely distributed in temperate and tropical areas. For thousands of years, Cannabis sativa has been utilized as a medicine and for recreational and spiritual purposes.[1] Phytocannabinoids are a family of compounds that are found in some flowering plants (such as cannabis plant), which is known for its psychotogenic and euphoric effects;[2] the main psychotropic constituent of cannabis is Tetrahydrocannabinol (THC).[3] THC is one of the at least 113 recognized cannabinoids in C. sativa. The pharmacological effects of cannabinoids are a result of interactions between those compounds and cannabinoid receptors, CB1 and CB2, located in many parts of the human body[4].

  • Many people around the world believe that the drug should be readily available for both medical and recreational use; however governments around the world still have strict laws about its usage.
  • Each country has its own laws and regulations surrounding the drug; some places are more relaxed, whist others still believe the drug should be an illegal substance[5].

Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained popularity as a potential treatment for certain conditions[6] See below).

Types of medicinal cannabis products[edit | edit source]

Cannabis pills.jpeg

Cannabis is a complex plant comprising more than 500 constituents, including approximately 100 cannabinoids. The main active ingredients used for medical purposes are tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive part of cannabis that produces a ‘high’, and has been used to treat symptoms such as nausea, pain and muscle spasticity. CBD has no psychoactive properties, and has been used to treat several inflammatory disorders and epilepsy.[6]

Medicinal cannabis products can come in three main forms:

  1. Pharmaceutical: Natural and synthetic medical-grade products with standardized content. The three main products are:
    • Dronabinol: Synthetic form of THC[3]
    • Nabilone: Synthetic form of THC
    • Nabiximols: Chemically pure 50:50 mixture of TCH and CBD.
  2. Medicinal-grade herbal cannabis: Produced and processed in controlled standard conditions to a medical grade, free of adulterants, higher levels of CBD and other cannabinoids, and contains lower levels of THC. This is provided in herbal form, or processed as an oil, balm, capsule or pill.
  3. Herbal cannabis on the illegal market: Potentially unstable THC and CBD, and may contain adulterants.[7]

The Evidence[edit | edit source]

Evidence.jpeg

At present, the evidence base for the use of medicinal cannabis products is limited.[8] The current evidence base for the use of medicinal cannabis products is heterogeneous, comprising a small number of randomized clinical trials when stratified by condition, symptom or intervention type.[9] [7]These studies are of variable quality, including those with high risk of bias (eg incomplete outcome data), low statistical power, and short follow-up time.

  • Recent reviews and analyses indicate there may be some therapeutic benefits of medicinal cannabis products in certain conditions but further research on the treatment efficacy and longer term side effects are warranted.
  • Currently, most research and evidence on medicinal cannabis products have come from five clinical conditions: multiple sclerosis; palliative care; epilepsy; nausea and vomiting; and chronic non-cancer pain.[7]
  • As there is limited scientific evidence to support the use of medicinal cannabis in most conditions, and in many cases the evidence is for its use together with other medicines, it should be used only when approved treatments have been tried and have failed to manage conditions and symptoms.[10]

Chronic Pain[edit | edit source]

The International Association for the Study of Pain (IASP) taskforce looked at all the available research published in peer-reviewed journals on the use of medicinal cannabis for pain management, from preclinical studies to human trials.

They concluded overall the studies’ “quality, rigour, and transparency of reporting” of benefits and harms needs to be improved across the board. The IASP taskforce demands higher quality data, for example through randomized controlled trials, to determine the safety and efficacy of using medicinal cannabis for pain[11]

Multiple sclerosis[edit | edit source]

Anout 50% of the studies in a recent systematic reviews showed that medicinal cannabis products may be effective for pain, spasticity, sleep and bladder function. The other half had inconclusive results.[7]

Epilepsy[edit | edit source]

A number of studies have found low evidence for the use of medicinal cannabis products for the treatment of paediatric epilepsy, and for patients up to aged 25 years, especially when first-line treatments (ie anti-epileptic drugs) have been found to be ineffective. The numbers needed to treat are as follows:

  • 50% or greater reduction in seizure frequency: 8
  • Complete seizure freedom: 17
  • Improvement in parental-reported quality of life: 5
  • The numbers needed to harm for any adverse event was 3, and serious adverse event was 23.

Palliative care[edit | edit source]

The use of medicinal cannabis products in palliative care is currently unclear.

Pain stress brain.png

Nausea and vomiting[edit | edit source]

A small number of studies have found relief of nausea and vomiting in patients with cancer who are undergoing chemotherapy; however, the evidence is lacking and some were compared with now out-of-date practices.

Chronic non-cancer pain[edit | edit source]

There is some evidence available for the treatment of neuropathic pain using medicinal cannabis products; however, the magnitude of effect is small. One systematic review found that the numbers needed to treat was 22 for a 30% reduction and 26 for a 50% reduction in self-reported pain intensity[7]

Side Effects[edit | edit source]

Like all prescription medicines, medicinal cannabis products can have side effects. The extent of effects of these can vary with the type of medicinal cannabis product and between individuals.

  • In general, the side effects of CBD-rich products are less than those for high-THC products, but because the required doses for CBD can be quite high in conditions such as pediatric epilepsies, a proportion of patients encounter side-effects with these CBD doses.
  • The known side-effects from medicinal cannabis treatment (both CBD and THC) include fatigue and sedation, vertigo, nausea and vomiting, fever, decreased or increased appetite, dry mouth, and diarrhea.
  • THC (and products high in THC) have been associated with convulsions, feeling high or feeling dissatisfied, depression, confusion, hallucinations, paranoid delusions, psychosis, and cognitive distortion (having thoughts that are not true)[10].

Relevance to Physical Therapy[edit | edit source]

Physiotherapists should be able to educate patients on the reported benefits of cannabis (eg chronic pain, MS, spasticity, and chemotherapy-induced nausea and vomiting) as well as potential adverse effects. Also, trends in the medical use of cannabis can be studied in relation to the extant laws of the country of practice to understand what is allowed in a region concerning the use of medicinal cannabis.

Summary of Evidence by Condition[edit | edit source]

Condition Products Current evidence quality
Multiple sclerosis
Pain Dronabinol, THC extracts Low to high and inconsistent
Disability and its progression None
Spasticity Nabiximols and THC:CBD Low and inconsistent
Bladder function None
Ataxia and tremor None
Sleep None
Quality of life Nabiximols and THC:CBD Low and inconsistent
Epilepsy
To reduce and/or eliminate the number of seizures CBD when used in conjunction with anti-epileptic drugs Low to very low
Oral cannabis extracts (OCEs) Very low
CBD:THC Very low
Cannabis sativa Very low
Quality of life CBD Low
Oral cannabis extracts (OCEs) Very low
CBD:THC Very low
Cannabis sativa Very low
THC Very low
Palliative care
Alzheimer's disease Dronabinol Unclear
Advanced cancer symptom control Dronabinol, THC:CBD, THC Unclear but some evidence against use
Cannabis sativa Unclear
Nabilone Unclear
Nausea and vomiting
Dronabinol Low to moderate
Nabilone Very low to moderate
THC Low, insufficient evidence
Levonantradol Low to moderate
THC:CBD Insufficient evidence
Cannabis sativa extract Unclear
Naximols Insufficient evidence
Chronic non-cancer pain
Nabiximols Moderate to high
Dronabinol Low to moderate
Nabilone Very low
Cannabis sativa Very low
THC extract Moderate
THC:CBD extract Low to moderate
Ajulemic acid Very low

Nabiximols is a TGA-registered medicine, under the tradename Sativex. It is a standardised extract of cannabis, containing roughly equal amounts of THC and CBD.

Dronabinol is a synthetic form of THC.

Nabilone is a cannabinoid synthesised in the laboratory, and has actions similar to THC although its chemical structure is different.

Ajulemic acid is a cannabinoid synthesised in the laboratory. It is similar to a breakdown product (metabolite) of THC but does not have psychoactive properties.[10]

References[edit | edit source]

  1. ↑ Maule WJ. Medical uses of marijuana (Cannabis sativa): fact or fallacy?. British journal of biomedical science. 2015 Jan 1;72(2):85-91.
  2. ↑ Gülck T, Møller BL. Phytocannabinoids: origins and biosynthesis. Trends in Plant Science. 2020 Jul 6.
  3. ↑ 3.0 3.1 PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 16078, Dronabinol; [cited 2022 Jan. 29]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Dronabinol
  4. ↑ Breijyeh,Z.;Jubeh,B.Bufo, S.A.; Karaman, R.; Scrano, L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses.Toxins 2021, 13, 117. Available from: https://res.mdpi.com/d_attachment/toxins/toxins-13-00117/article_deploy/toxins-13-00117.pdf (accessed 5.4.2021)
  5. ↑ best in Au Where is cannabis legal Available from:https://bestinau.com.au/marijuana-laws-from-around-the-world-where-is-cannabis-legal/ (accessed 5.4.2021)
  6. ↑ 6.0 6.1 Argueta DA, Ventura CM, Kiven S, Sagi V, Gupta K. A balanced approach for cannabidiol use in chronic pain. Frontiers in pharmacology. 2020 Apr 30;11:561.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 RACGP Medicinal Cannabis Available from:https://www.racgp.org.au/advocacy/position-statements/view-all-position-statements/clinical-and-practice-management/medical-cannabis (accessed 5.4.2021)
  8. ↑ O’Brien K. Medicinal cannabis: Issues of evidence. European Journal of Integrative Medicine. 2019 Jun 1;28:114-20.
  9. ↑ Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV. Cannabinoids for medical use. JAMA [Internet]. 2015; 313 (24): 2456.
  10. ↑ 10.0 10.1 10.2 Aust Government Guidance on medicinal cannabis Available from:https://www.tga.gov.au/publication/guidance-use-medicinal-cannabis-australia-patient-information (accessed 5.4.2021)
  11. ↑ IASP Position Statement on the Use of Cannabinoids to Treat Pain Available from:https://www.iasp-pain.org/PublicationsNews/NewsDetail.aspx?ItemNumber=11145&navItemNumber=643 (accessed 5.4.2021)
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