Medicinal Cannabis (MC) and Cannabis-Based Medicin= es (CbMs) for Acute and Chronic Pain Treatment: A Review Article

Cannabis medicinal (MC) y medicamentos a base de cannabis (CBM) para el tratamiento = del dolor agudo y crónico: un artículo de revisión

Roberto David Flores Núñez

https://orcid.org/0000-0002-7893-0756

Investigador independiente, Qui= to, Ecuador

flores.d.roberto.n@gmail.com &nbs= p; &= nbsp; =

&n= bsp;	= Artículo de Investigación Científica y Tecnológica= = Enviado: 15/11/2022 = Revisado: 28/12/2022 = Aceptado: 15/01/2023 = Publicado:18/08/2023 DOI: https://doi.org/10.33262/= ap.v5i3.1.383 <= /span>
<= span style=3D'font-size:11.0pt;mso-bidi-font-size:12.0pt;line-height:115%; font-family:"Times New Roman",serif;mso-fareast-font-family:Calibri; color:blue;mso-font-kerning:0pt;mso-ligatures:none'>	=
= = Cítese:	=	= Flores Núñez, R. D. (2023). Medici= nal Cannabis (MC) and Cannabis-Based Medicines (CbMs) for Acute and Chronic P= ain Treatment: A Review Article. AlfaPublicaciones, 5(3.1), 32–46. https://d= oi.org/10.33262/ap.v5i3.1.383 =
<= !--[if gte vml 1]>		= ALFA PUBLICACIONES, es una Revista Multidisciplinar, Trimestral, que se publicará en soporte electrónico tiene como misión contribuir a la formación de profesionales competentes con visión humanística y crítica que sean capaces de exp= oner sus resultados investigativos y científicos en la misma medida que= se promueva mediante su intervención cambios positivos en la sociedad= . https://alfapublicaciones.com= La revista es editada po= r la Editorial Ciencia Digital (Editorial de prestigio registrada en la Cámara Ecuatoriana de Libro con No de Afiliación 663) www.celibro.org.ec
		= Esta revista está protegida bajo una licencia Creative Commons AttributionNonCommercialNoDerivatives 4.0 International. Copia de la licencia: http://creativecommons.org= /licenses/by-nc-nd/4.0/=
= Palabras claves: = Cannabis Medicinal (= MC), Cannabidiol (CBD), Medicamentos a Base de Cannabis (CBM), Δ9 -tetrahydrocannabinol (THC), Dolor crónico, cannabinoides.=	=	Resumen Introducción: Cannabis ha sido vastamente us= ado con fines medicinales por siglos debido a sus propiedades analgési= cas. Evidencia científica sugiere que el cannabis medicinal posee un gr= an potencial para el tratamiento del dolor agudo y crónico. Sin embar= go, los resultados has sido inconsistentes. Objetivos: Hacer una revisión sobre la eficacia del cannabis medicinal y de los medicamentos a base de cannabis para el tratamiento del dolor agudo y crónico de cualquier origen. Metodología: Google Sch= olar y PubMed fueron usados para encontrar ensayos clínicos aleatorizad= os, doble ciego, y controlados con placebo de casos de dolor agudo y crónico. Resultad= os: Solo cuatro de los once ensayos clínicos que formaron parte de este artículo de revisión encontraron beneficios del tratamiento= a base de cannabis para reducir el dolor crónico. Mientras que siete ensayos clínicos revelaron que el cannabis medicinal y los medicamentos a base de cannabis no tienen una mayor eficacia que el tratamiento de placebo. Conclusiones: El cannabis medicinal y los medicamentos a base de cannabis podrían ser de gran ayuda como medicina complementaria. Area de estudio general: = Medici= na Area de estudio especifica: Algesi= ologia=
Keywords: Medicinal Cannabis (MC), Cannabidiol (CBD), Cannabis-Based Medicin= es (CBM), Δ9 -tetrahydrocannabinol (THC), Chronic Pain, cannabinoids.		Abstract Introduction: Cannabis has been used for medicin= al purposes for centuries due to its analgesic properties. Some evidence suggests that cannabis has an enormous potential for acute and chronic pa= in management. However, the results have been inconsistent. Objectives: To review the quality of the data gathered over the years about medicinal cannabis and cannabis-based medicines to discover the analgesic efficacy = of using cannabis for acute and chronic pain. Methodology: Google Sch= olar and PubMed were used to find randomized, double-blinded, placebo-controll= ed reports of acute and chronic pain cases of any origin. Results: On= ly four out of eleven studies that took part in this review found some beneficial outcomes of the cannabis treatment. Seven studies revealed that medicinal cannabis and cannabis-based medicines were no better than the placebo treatment. Conclusions: Medicinal cannabis and cannabis-ba= sed medicines may be useful when used as an adjunctive medicine. <= /span> General area of study: Medicine Specific area of study: Algesiology

Introduction

Despite its wide variety of practical uses in diff= erent fields, cannabis production and manipulation have been themes of considerable contr= oversy for many decades. According to Crocq (2022), it has been estimated that the= use of cannabis dates around 11,700 years ago. The plant itself seems to be originated from Central Asia (Afghanistan, Mongolia, Pakistan) where it was domesticated to produce strains which were later used either as fibers or a= s a psychotropic drug. Then, it was spread all over Europe and Asia by nomadic people. Furthermore, it has been argued that cannabis was anciently used as= a medicinal herb to treat loss of appetite, sleeping disorders, anxiety, dive= rse types of pain and nausea in some countries, such as India, China, Egypt, and Greece (Crocq, 2022). Despite its popularity in other Asian countries, it w= as not until the late 19^th and early 20^th century when cannabis became popular in Western countries. Crocq (2022) argues that Empr= ess Elisabeth of Austria and Queen Victoria consumed cannabis to treat menstrual cramps, increase appetite and relieve cough. However, cannabis eventually b= ecame a subject of stigmatization in many Western countries in the mid-20^{th<=
/sup>
century (Rull, 2022). As many restrictions were introduced in the US; the
Marihuana Tax Act was passed to regulate the use and possession of cannabis=
in
1937. Therefore, cannabis was later removed from the US Pharmacopeia (Savag=
e et
al., 2016). Yet, some people argue that the decision to make cannabis illeg=
al in
the US seems to be based on racist beliefs. Smith et al. (2022) indicates t=
hat cannabis
was commonly associated with the African American and Hispanic communities =
in
1923. Therefore, the stigmatization and later illegalization of cannabis le=
d to
a misconception of the plant’s properties and a lack of research
opportunities. As a result, the medicinal properties of cannabis remained
unknown for many years. Nevertheless, researchers’ fascination about =
the therapeutic
properties of the plant persisted over time. Due to its enormous pharmaceut=
ical
potential, cannabis has undergone a process of destigmatization in recent y=
ears.
The legalization of cannabis production in the US, Canada and some European
countries has increased the interest of conducting research and finding new
industrial and medicinal applications. Recent evidence suggests that
cannabis-based medicines may be effective in reducing pain and alleviating
symptoms of patients who suffer from insomnia, epilepsy, multiple sclerosis
(MS) and cancer (Kleckner et al., 2019). The first prescription drug derived
from cannabis was approved by the US Food and Drug Administration (FDA) in
2018. Epidyolex became the first ever commercially available}cannabis-based medicine, and its main function is to treat epilepsy (MacCallum & Ru= sso, 2018). Nowadays, the most common prescribed cannabis-based medicines are: N= abiximols (Sativex), Nabilone and Epidyolex. Nabilone is commonly used to treat the s= ide effects of chemotherapy, whereas Nabiximols is often used for the treatment= of multiple sclerosis (MS). Even though cannabis is = legal for medicinal and recreational purposes in some states in the US, it is sti= ll listed as a Schedule I drug by the Food and Drug Administration (FDA) for i= ts capability to cause intoxication and abuse. On the other hand, researchers have been a= ble to make some important discoveries about cannabis. It has been determined t= hat cannabis consists of two main subspecies: C. sativa and C. indica= . The difference between these two principal taxonomic groups is in their geographical origins. C. sativa originates from India, whereas C. indica had origins in Afghanistan (McPartland & Small, 2020). Furth= ermore, years of arduous research has led us to the findings of two crucial compone= nts of cannabis: the endocannabinoid system (ECS) and cannabinoids. The endocannabinoid system (ECS) consists of receptors that can be found in our body, particularly in our brain. The main purpose of the ECS is to regulate= the brain’s cognitive and behavioral functions. While cannabinoids are ac= tive biochemical substances which can bind to the cannabinoid receptors of the b= rain (Fisher et al., 2021). When cannabinoids reach the endocannabinoid system, = they could alter our behavior (Young & Denovan-Wright, 2022). In addition, it has been discovered that cannabis contains more than 120 cannabinoid compou= nds. Navarro et al. (2022) states that two of the most bioactive compounds are Δ⁹ -tetrahydrocannabinol (THC) and cannabidiol (CBD). Altho= ugh THC and CBD are both found in the cannabis plant, they have different chemi= cal structures and properties. THC is often attributed all the psychoactive properties (Stella, 2023). It is believed that CBD and THC might be benefic= ial for the treatment of acute and chronic pain. Chronic pain is a condition wh= ich can cause enduring physical pain and disability and could last more than 3 months. It is estimated that 20% of the population around the world are affected by chronic pain (Dykukha et al., 2021). Despite the growing eviden= ce about the therapeutic properties and health benefits of medicinal cannabis = and cannabis-based medicines for acute and chronic pain management, there seems= to be some inconsistencies in those findings and some scientists claim that cannabis-based medicines do not improve a patient’s overall wellbeing= . For this reason, it is especially important to critically analyses the existing= literature and evaluate the effectiveness of medicinal cannabis and cannabis-based medicines. In this review, the advantages, and disadvantages of using cannabis-based medicines and medicinal cannabis to treat acute and chronic = pain will be discussed. The principal objective of this research is to evaluate = the veracity and quality of existing findings and try to discover whether canna= bis-based medicines and medicinal cannabis could be beneficial for patients who suffer from acute and chronic pain or not.

Materials and method

Google Scholar and PubMed were used to find double= -blind, randomized, placebo-controlled clinical trials of medicinal cannabis and ca= nnabis-based medicines for the treatment of acute and chronic pain of any origin. Due to= the extremely limited research data, I decided to expand the range of time of t= he randomized trials publications since its inception until 2023. I summarized data concerning the type of delivery method (oral, smoking and vaporization) delivery options, number of participants, age, gender, comorbidities, durat= ion of the clinical trial, type of intervention, dosing, outcomes, health benefits= and adverse effects of the treatment. I excluded review articles and other secondary papers. I only selected reports written in English. I used the following keywords: “double-blind,” “randomized,” “placebo-controlled clinical trials,” “chronic pain,̶= 1; “cannabis,” “cannabinoids,” “cannabis-based medicines” to find the eligible clinical reports. I only selected 11 reports out of many articles. I excluded cannabis-dependent patients’= cases. I focused only on cannabis-based medicines and medicinal cannabis products = to treat pain-inducing diseases of any origin.

Results

Table 1

Summary of the patient demographics= in the selected case studies

Reference<= /o:p>

Number of Patie= nts(n)

Country

origin:

Gender

Mean age (years= )

Comorbidities:

Pain Diagnosis:=

Previous Cannabinoids Use:

Amount of Cannabis use per month (g)<= /span>

mean BMI (Kg/m2= )

Concurrent Medi= cations:

Chaves et al. 2= 020

Brazil

All Female

51.9=

Depression and Anxiety

Chronic musculoskeletal pain

None

Unknown

Antidepressants= , benzodiazepines, opioids

Almog et al. 20= 20

Israel

19 Male and 8 Female

48.3=

Diabetes

Chronic pain, phantom/stump pain, diabetic neuropathy

Yes<= /span>

16-30

27.8=

Antidepressants, benzodiazepines, anticonvulsants, analgesics, opioids

Abrams et al. 2= 020

USA<= /span>

10 Male and 13 Female

37.6=

Unknown

Chronic pain wi= th acute vaso-occlusive crisis

Yes<= /span>

Unknown

Analgesics,

Opioids

Van de Donk et al. 2019

Netherlands

All Female

39.13

None

Chronic Pain

None

29.7=

Paracetamol and Ibuprofen

Selvarajah et a= l. 2010

United Kingdom<= o:p>

19 male and 11 female

58.2=

Depression

Chronic painful= DPN

Yes<= /span>

Unknown

31.9=

Antidepressants=

Narang et al. 2= 023

USA<= /span>

35 Male and 55 Female

Kidney/ureteral stones

Post-Ureterosco= py pain

None

Oxycodone, tamsulosin, oxybutynin, phenazopyridine

Ware et al. 201= 0

Canada

9 Male and 12 female

45.4=

Allodynia, hyperalgesia

Chronic neuropa= thic pain

None

Unknown

Antidepressants, anticonvulsants,

Anesthetics,

opioids

Turcotte et al.= 2015

Canada

2 Male and 13 female

45.5=

None

Chronic neuropa= thic pain

None

Unknown

Gabapentin (GBP= )

Lynch et al. 20= 14

Canada

3 Male and 15 female

Allodynia, hyperalgesia, hypesthesia<= /span>

Chemotherapy-in= duced neuropathic pain

Unknown

Analgesics, placitaxel, vincristine, cisplatin

Table 1

Summary of the patient demographics= in the selected case studies (continuation)

Reference<= /o:p>

Number of Patients(n)

Country

origin:

Gender

Mean age (years= )

Comorbidities:

Pain Diagnosis:=

Previous Cannabinoids Use:

Amount of Cannabis use per month (g)<= /span>

mean BMI (Kg/m2= )

Concurrent Medications:

Bebee et al. 20= 21

100<= /span>

Australia<= /o:p>

56 male and 44 female

None

Acute non-traum= atic musculoskeletal pain

None

Unknown

Analgesics, oxycodone, paracetamol

Lichtman et al. 2018

397<= /span>

USA, Germany,

Belgium,

Hungary, Poland, the UK

214 male and 183 female

59.2=

Depression, pancytopenia, pulmonary embolism, pneumonia

Chronic Pain

Unknown

26.8=

Morphine

Table 1 summarizes some of the patients’ demographics. M= ost patients that participated in these clinical trials were adults, some of th= em suffer from major comorbidities such as: depression, pneumonia, anxiety, et= c.

Table 2

Summary of the diagnosis, study met= hod and treatment details and outcomes of all patients

Reference:

Diagnosis:

Method:

Treatment:

Results:

Chaves et al. 2020

Fibromyalgia

Double-blinded, randomized, placebo-controlled

Ingested a few drops of cannabis-rich oil (24.44 mg/ml of THC and = 0.51 mg/ml of CBD)

There was a significant improvement on pain relief and a decrease = in FIQ score in the cannabis group

Almog et al. 2020

Radiculopathy,

diabetic neuropathy, CRPS, phantom/stump pain

Double-blinded, randomized, placebo-controlled,<= /p>

cross-over

Inhaled one of three doses of 0.5 mg, 1.0 mg of THC or placebo

There was a significant pain reduction compared to the placebo gro= up

Abrams et al. 2020

Sickle-Cell Disease

Double-blinded,

randomized, placebo-controlled

Inhaled vaporized cannabis 3 times daily for a 5-day period (4.4% = of THC and 4.9%CBD)

There was not statistically significance in reduction of pain betw= een the cannabis and placebo groups

Van de Donk et al. 2019

Fibromyalgia

Double-blinded, randomized, placebo-controlled,<= /p>

4-way crossover

Inhaled vaporized cannabis of 4 distinct varieties

There was no significant pain reduction compared to the placebo gr= oup

Selvarajah et al. 2010

Diabetic neuropathy

Double-blinded, randomized, placebo-controlled

Sprayed Sativex (27 mg/ml of THC and 25mg/ml of CBD) four times a = day

There was no significant pain reduction compared to the placebo gr= oup

<= o:p>

Table 2

Summary of the diagnosis, study met= hod and treatment details and outcomes of all patients (continuation)

Reference:=

Diagnosis:

Method:

Treatment:

Results:

Narang et al. 2023

Urinary Calculi

Prospective, double-blinded, randomized, placebo-controlled

Ingested 20 mg of CBD oil (Epidiolex) for 3 days=

There was no significant pain reduction compared to the placebo gr= oup

Ware et al. 2010

Chronic neuropathic pain caused by surgery or trauma

Double-blinded, randomized, placebo-controlled,<= /p>

Four-period crossover

Inhaled 25 mg of 0%, 2.5%, 6% and 9.4% THC three times daily for 14 days

There was a significant improvement on pain relief in the cannabis group

Turcotte et al. 2015

Multiple Sclerosis

Double-blinded, randomized, placebo-controlled

Ingested (0.5mg/week increase) and 2mg a day of Nabilone for 5 wee= ks

There was a significant improvement on pain relief in the cannabis group

Lynch et al. 2014

Cancer

Double-blinded, randomized, placebo-controlled,<= /p>

crossover

12 Sprays of Nabiximols (Sativex) per day for four weeks

There was not statistically significance in reduction of pain betw= een the cannabis and placebo groups

Bebee et al. 2021

Acute low back pain

Double-blinded, randomized, placebo-controlled

Ingested 400 mg of CBD

There was no significant pain reduction compared to the placebo gr= oup

Lichtman et al. 2018

Cancer

Double-blinded, randomized, placebo-controlled

Sprayed Nabiximols (27mg/ml of THC and 25mg/ml of CBD) for five we= eks

There was not a significant difference between the placebo and the cannabis group, but some participants benefited from the cannabis treatme= nt in the secondary endpoint

As it can be seen from table 2., seven studies sho= wed no overall improvement in chronic pain alleviation. Conversely, only four stud= ies showed a significant improvement, whereas only 1 study revealed that 1 cann= abis group slightly ameliorate some of the symptoms of chronic pain but there wa= s no overall positive effect of the cannabis treatment compared to placebo. To a= void risk of bias, all the research methods were double-blinded, randomized and placebo-controlled.

Discussion

Some review articles point out that CBD and THC mi= ght have a more positive effect compared to placebo when dealing with acute and chronic pain. In his systematic review article, Dykukha et al. (2021) argues that nabiximols was more effective than placebo for chronic neuropathic pain alleviation; this review article included 1289 participants. In addition, a meta-analysis was performed to obtain a more accurate statistical interpretation of the results. Therefore, these findings are statistically = dependable. Whereas some studies indicate that cannabis-based medicines may be successf= ul when used as an adjuvant therapy. Haleem & Wright (2020) indicate that herbal cannabis and cannabis-based medicines may be efficacious to treat patients who suffer from advanced stages of cancer. Furthermore, it was discovered that when Nabilone was used as an adjuvant therapy, it could not= ably reduce pain (Tsang & Giudice, 2016). Moreover, a doble-blinded, randomi= zed, placebo-controlled trial in patients with fibromyalgia. 17 patients followe= d a treatment with THC-rich cannabis oil. The results of this study showed that there was significant reduction in pain (Chaves et al., 2020). Likewise, a crossover, randomized, placebo-controlled, double-blinded clinical trial was conducted with diabetic neuropathy and radiculopathy patients to evaluate t= he efficacy of THC. The study consisted in inhaling small doses of 0.5 mg- 1.0= mg of THC. As a result, pain was significantly reduced compared to placebo (Al= mog et al., 2020). Similarly, in a crossover, four-period, double-blinded, randomized, placebo-controlled clinical trial, a cannabis treatment demonstrates its efficacy. Twenty-one chronic neuropathic pain patients inh= aled 25mg of herbal cannabis for 14 days. The treatment showed favorable results= . As a consequence, the analgesic properties of cannabis proved to be advantageo= us when dealing with chronic pain (Ware et al., 2010). Besides, the efficacy of Nabilone was also analyzed in a randomized, double-blinded, placebo-control= led clinical trial in multiple sclerosis patients. Nabilone was used as an adjunctive to Gabapentin. The Nabilone group showed greater results and was more successful when it was used in combination with Gabapentin in alleviat= ing discomfort than the placebo group. Thus, these results further contribute to the hypothesis that cannabis-based medicines may be useful as an adjunctive the= rapy (Turcotte et al., 2015).

On the other hand, some other authors argue that c= annabinoids might be ineffective for chronic pain treatment. In another systematic literature review, which included 1352 individuals; it was found that eight= out of thirteen randomized placebo-controlled trials, cannabis-based medicines = appear to have a minimal or no analgesic effect for chronic pain management. Howev= er, the authors also pointed out that cannabinoids’ analgesic properties coul= d be useful for the treatment of pain of any origin and further exhaustive resea= rch was recommended (Longo et al., 2021). Furthermore, some other review articles c= laim that cannabis is not effective for pain relief. A systematic review on canc= er pain evaluated the efficacy of cannabis-based medicines and medical cannabi= s. It was found that in 1534 cancer patients, THC and Nabiximols did not reduce pain compared to placebo (Haeuser et al., 2019). Nevertheless, some placebo-controlled studies suggest that nabilone might alleviate noncancer = pain (Tsang & Giudice, 2016). In addition, in a randomized, doble-blinded, placebo-controlled trial in Sickle-cell disease patients determined that cannabis was statistically no better than placebo in reducing painful sympt= oms and improving the quality of life. In this clinical trial, participants had= to inhale various doses of vaporized cannabis 3 times daily (Abrams et al., 20= 20). Besides, a 4-way-crossover, randomized, double-blinded, placebo-controlled trials with fibromyalgia patients to assess the effectiveness of vaporized cannabis for the treatment of chronic pain. These findings suggest that medicinal cannabis might not be as powerful as placebo (Van de Donk et al.,= 2019). Additionally, a randomized, double-blinded, placebo-controlled study for the analysis of Sativex in diabetic neuropathic patients. It was demonstrated t= hat Sativex was no better than placebo in clinical trials (Selvarajah et al., 2010). Similarly, a prospective, randomized, double-blinded, placebo-contro= lled study was designed to evaluate the benefits of Epidiolex. Participants who underwent a ureteroscopy procedure took part in this study. Patients had to ingest CBD oil (Epidiolex) for three days. The authors concluded that there= was no outstanding difference in pain reduction between the cannabis and the pl= acebo treatments. Therefore, administrating cannabis to these patients did not re= duce pain considerably compared to the placebo treatment (Narang et al., 2023). = Correspondingly, in another randomized, placebo-controlled, crossover, pilot trial, Nabiximo= ls (Sativex) was used to treat chemotherapy-induced neuropathic pain in 18 patients. The results of this study revealed that there was no remarkable distinctive outcome between the Nabiximols and the placebo groups. However,= only five participants registered a reduction of pain in a responder analysis (L= ynch et al., 2014). In addition, a randomized, double-blinded, placebo-controlled trial estimated the analgesic efficacy of CBD as an adjunct medication in patients with acute low-back pain. It was found that the CBD treatment was = not better than the placebo treatment (Bebee et al., 2021). Finally, another randomized, double-blinded, placebo-controlled trial of Nabiximols in cancer patients obtained some comparable results from previous studies. The outcom= e of the Nabiximols treatment was not more successful than the placebo treatment= in alleviating chronic pain. Nevertheless, in the secondary endpoint of this study, there were some patients that benefited from the Nabiximols treatmen= t (Lichtman et al., 2018). According to Fisher et al. (2021), there was a 30% of pain reduction in cancer patients. Whereas two placebo-controlled trials showed = 50% pain relief in 464 patients. However, the quality of this data was extremely poor. As a result, the authors concluded that there was no overall analgesic effect when the treatment lasted more than seven days (Fisher et al., 2021)= . Therefore, it appears that medicinal cannabis and cannabis-based medicines are not efficient enough to alleviate discomfort and improve the quality of life of chronic and acute pain patients.

In the contrary, some studies also claim that cann= abis-based medicines might have some adverse events. For instance, the use of Nabilone= is associated with adverse reactions such as dizziness, euphoria, and drowsine= ss (Tsang & Giudice, 2016). Moreover, THC has been contraindicated due to some studies involving randomized clinical trials with rodents which concluded t= hat cannabis might cause some mayor harmful effects. In addition, the use of ca= nnabis-based medicines has been restrained during pregnancy and lactation. Whereas cardi= ac conditions and psychosis are also listed as contraindications to the use of cannabis (MacCallum & Russo, 2018). Nevertheless, it has been demonstra= ted that cannabis do not cause overdose and do not represent an elevated risk of addiction (Savage et al., 2016). Nonetheless, there are some evidence that suggests that cannabis may cause addiction. Chronic THC exposure increases = the risk of addiction due to changes in neuron morphology. Furthermore, there appears to be some amygdala volumetric and morphological differences between cannabis users and non-cannabis users; these morphological changes might be linked to cannabis use disorder (Zehra et al., 2018). Furthermore, Hill et = al. (2022) point out that cannabis abuse might be potentially harmful to psychiatric patients and adolescents. Early exposure to cannabis with high = THC content may negatively affect hippocampus development during adolescence and prenatal periods. Contrastingly, there has been a lot of concern about the effects of higher potency and dosage of non-medical cannabis products since= the legalization of cannabis in North America. High potency cannabis products c= an be described as products which have high THC content. As cannabis became le= gal, the availability of higher potency cannabis products increased over the past few years. Even though causality has not been fully determined, Matheson &a= mp; Le Foll (2020), argue that cannabis may be associated with psychosis and a portion of cannabis users might develop cannabis use disorder (CUD); howeve= r, it is estimated that only 1 out of 10 cannabis users might develop this condition. Cannabis use disorder (CUD) can be defined as a type of conditio= n when a dependence on cannabis is acquired over a prolonged period which can caus= e intoxication, great distress, and difficulty to complete daily activities (Patel & Marwaha, 2020). Moreover, there seems to be a genetic predisposition for cannabis use disorder (CUD).= A large genome-wide association study (GWAS) has shown that CUD is positively correlated with other psychopathologies (Johnson et al., 2020). Some other studies have found a minor difference in the volume of grey matter between cannabis users and cannabis dependent users, but these results have been inconsistent. Another drawback of using cannabis is its effect on heart rat= e. On the other hand, cannabis appears to be less harmful compared to other drugs such as tobacco and alcohol. For these reasons, i= t is necessary to keep all cannabis users informed about the possible risks of consuming h= igh potency cannabis products during prolonged periods of time and educate cons= umers about using the precise dosage to avoid any type of intoxication. Further research is needed to find if there are significant physiological differenc= es between cannabis users and non-cannabis users.

Conclusion

· These results are consist= ent with other review articles that claimed that there was not a significant difference between the cannabis and the placebo treatments. More research is needed to obtain a more in-depth understanding of the medicinal properties = of cannabinoids. Furthermore, medicinal cannabis and cannabis-based medicines = seem to have a potential as adjunctive therapies. It is crucial to perform more research, so that physicians and the public could be better informed for cannabis-based issues and contraindications.

Conflict of interest:

There is no conflict of interest.

References

Abrams, D. I., Couey, P., Dixit, N., Sagi, V., H= agar, W., Vichinsky, E., & Gupta, K. (2020). Effect of inhaled cannabis for p= ain in adults with sickle cell disease: a randomized clinical trial. JAMA network open, 3(7), e2010874-e2010874. https://jam= anetwork.com/journals/jamanetworkopen/article-abstract/2768349

Almog, S., Aharon‐Peretz, J., Vulfsons, S., Ogintz, M., Abalia, H., Lupo, T., &a= mp; Eisenberg, E. (2020). = The pharmacokinetics, efficacy, and safety of a novel selective‐dose cann= abis inhaler in patients with chronic pain: a randomized, double‐blinded, placebo‐controlled trial. European journal of pain, 24(8), 1505-1516.= https:/= /onlinelibrary.wiley.com/doi/full/10.1002/ejp.1605

Bebee, B., Taylor, D. M., Bourke, E., Pollack, K= ., Foster, L., Ching, M., & Wong, A. (2021). The CANBACK trial: a randomis= ed, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain. Medical Journal of Australia, 214(8), 370-375. https:/= /onlinelibrary.wiley.com/doi/full/10.5694/mja2.51014<= /span>

Chaves, C., Bittencourt, P. C. T., & Pelegri= ni, A. (2020). Ingestion of a THC-rich cannabis oil in people with fibromyalgia: a randomized, double-blind, placebo-controlled clinical trial. Pain Medicine, 21(10), 2212-2218. <= span style=3D'color:windowtext;text-decoration:none;text-underline:none'>https:/= /academic.oup.com/painmedicine/article/21/10/2212/5942556

Crocq, M. A. (2022). History of cannabis and the endocannabinoid system. Dialogues in clinical neuroscience. https:/= /www.tandfonline.com/doi/full/10.31887/DCNS.2020.22.3/mcrocq

Dykukha, I., Malessa, R., Essner, U., & Überall, M. A. (2021). Nabiximols in chronic neuropathic pain: a meta-analysis of randomized placebo-controlled trials. Pain Medicine, 22(4), 861-874. https:/= /academic.oup.com/painmedicine/article/22/4/861/6131796?login=3Dfalse

Fisher, E., Moore, R. A., Fogarty, A. E., Finn, = D. P., Finnerup, N. B., Gilron, I., & Eccleston, C. (2021). Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic rev= iew of randomised controlled trials. Pain, 162, S45-S66. https://journals.lww.com/pain/Fulltext/2021/0700= 1/Cannabinoids,_cannabis,_and_cannabis_based.5.aspx

Haeuser, W., Welsch, P., Klose, P., Radbruch, L., & Fitzcharles, M. A. (2019). Efficacy, tolerability, and safety of cannabis-based medicines for cancer pain: A systematic review with meta-analysis of randomised controlled trials. Schmerz (Berlin, Germany), 33(5), 424-436. https://europepmc.org/article/med/31073761

Haleem, R., & Wright, R. (2020). A scoping r= eview on clinical trials of pain reduction with cannabis administration in adults. Journal of clinical medicine research, 12(6), 344. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC729= 5551/

Hill, K. P., Gold, M. S., Nemeroff, C. B., McDon= ald, W., Grzenda, A., Widge, A. S., ... & Carpenter, L. L. (2022). Risks and benefits of cannabis and cannabinoids in psychiatry. American Journal of Psychiatry, 179(2), 98-109. https:/= /ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2021.21030320

Johnson, E. C., Demontis, D., Thorgeirsson, T. E= ., Walters, R. K., Polimanti, R., Hatoum, A. S., & Wang, J. C. (2020). A l= arge-scale genome-wide association study meta-analysis of cannabis use disorder. The Lancet Psychiatry, 7(12), 1032-1045.

Kleckner, A. S., Kleckner, I. R., Kamen, C. S., Tejani, M. A., Janelsins, M. C., Morrow, G. R., & Peppone, L. J. (2019). Opportunities for cannabis in supportive care in cancer. Therapeutic advanc= es in medical oncology, 11, 1758835919866362. https://journals.sagepub.com/doi/full/10.1177/17= 58835919866362

Longo, R., Oudshoorn, A., & Befus, D. (2021). Cannabis for chronic pain: a rapid systematic review of randomized control trials. Pain Management Nursing, 22(2), 141-149. https://www.sciencedirect.com/science/article/ab= s/pii/S1524904220302253

Lichtman, A. H., Lux, E. A., McQuade, R., Rosset= ti, S., Sanchez, R., Sun, W., & Fallon, M. T. (2018). Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. Journal of pain and symptom management, 55(2), 179-188. = https://www.sciencedirect.com/science/article/pi= i/S0885392417304657

Lynch, M. E., Cesar-Rittenberg, P., & Hohman= n, A. G. (2014). A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. Journal of pain and symptom manageme= nt, 47(1), 166-173.https:/= /www.sciencedirect.com/science/article/pii/S0885392413002388

MacCallum, C. A., & Russo, E. B. (2018). Pra= ctical considerations in medical cannabis administration and dosing. European jour= nal of internal medicine, 49, 12-19. https://www.sciencedirect.com/science/article/ab= s/pii/S0953620518300049

Matheson, J., & Le Foll, B. (2020). Cannabis legalization and acute harm from high potency cannabis products: a narrative review and recommendations for public health. Frontiers in psychiatry, 11, 591979. https://www.frontiersin.org/articles/10.3389/fps= yt.2020.591979/full

McPartland, J. M., & Small, E. (2020). A classification of endangered high-THC cannabis (Cannabis sativa subsp. indi= ca) domesticates and their wild relatives. PhytoKeys, 144, 81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC714= 8385/

Narang, G., Moore, J., Wymer, K., Chang, Y. H., = Lim, E., Adeleye, O., & Stern, K. L. (2023). Effect of cannabidiol oil on post-ureteroscopy pain for urinary calculi: a randomized, double-blind, placebo-controlled trial. The Journal of urology, 209(4), 726-733. <= span style=3D'color:windowtext'>https://www.auajournals.org/doi/full/10.1097/JU.= 0000000000003139

Navarro, D., Gasparyan, = A., Navarrete, F., Torregrosa, A. B., Rubio, G., Marín-Mayor, M., ... & Manzanares, J. (2022). Molecu= lar alterations of the endocannabinoid system in psychiatric disorders. International journal of molecular sciences, 23(9), 4764.https://www.mdpi.com/1422-0067/23/9/4764

Patel, J., & Marwaha, R. (2020). Cannabis Use Disorder, StatPearls. Treasure Island (FL). [Google Scholar]. https://www.ncbi.nlm.nih.gov/book= s/NBK538131/

Rull, V. (2022). Origin, early expansion, domest= ication, and anthropogenic diffusion of Cannabis, with emphasis on Europe and the Iberian Peninsula. Perspectives in Plant Ecology, Evolution and Systematics, 125670. https://www.sciencedirect.com/science/article/pi= i/S1433831922000129

Savage, S. R., Romero-Sandoval, A., Schatman, M., Wallace, M., Fanciullo, G., McCarberg, B., & Ware, M. (2016). Cannabis = in pain treatment: clinical and research considerations. The Journal of Pain, 17(6), 654-668. https://www.sciencedirect.com/science/article/ab= s/pii/S1526590016005435

Selvarajah, D., Gandhi, R., Emery, C. J., & Tesfaye, S. (2010). Randomized placebo-controlled double-blind clinical tri= al of cannabis-based medicinal product (Sativex) in painful diabetic neuropath= y: depression is a major confounding factor. Diabetes care, 33(1), 128-130. https://diabetesjournals.org/care/article/33/1/1= 28/29741/Randomized-Placebo-Controlled-Double-Blind

Smith, A., Wong, N. D., Sørensen, A. R., = Jones, I., & Coraiola, D. M. (2022). Historical narratives and the defense of stigmatized industries. Journal of Management Inquiry, 31(4), 386-404. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://journals.sagepu= b.com/doi/pdf/10.1177/10564926211019481

Stella, N. (2023). THC and CBD: Similarities and differences between siblings. Neuron https://www= .sciencedirect.com/science/article/abs/pii/S0896627322011199

Tsang, C. C., & Giud= ice, M. G. (2016). Nabilone= for the Management of Pain. Pharmacotherapy: The Journal of Human Pharmacology and = Drug Therapy, 36(3), 273-286. https://accpjournals.onlinelibrary.wiley.com/doi= /full/10.1002/phar.1709

Turcotte, D., Doupe, M., Torabi, M., Gomori, A., Ethans, K., Esfahani, F., & Namaka, M. (2015). Nabilone as an adjunctiv= e to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Medicine, 16(1), 149-159. https://aca= demic.oup.com/painmedicine/article/16/1/149/2460271?login=3Dfalse

Van de Donk, T., Niester= s, M., Kowal, M. A., Olofsen, E., Dahan, A., & Van Velzen, M. (2019). <= span lang=3DEN-US style=3D'color:windowtext'>An experimental randomized study on= the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. Pain, 160(4), 860. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC643= 0597/

Ware, M. A., Wang, T., Shapiro, S., Robinson, A., Ducruet, T., Huynh, T., & Collet, J. P. (2010). Smoked cannabis for chr= onic neuropathic pain: a randomized controlled trial. Cmaj, 182(14), E694-E701. https://www.cmaj.ca/content/182/14/E694.full

Young, A. P., & Denovan-Wright, E. M. (2022). The dynamic role of microglia and the endocannabinoid system in neuroinflammati= on. Frontiers in Pharmacology, 12, 806417. https://www.frontiersin.org/articles/10.3389/fph= ar.2021.806417/full

Zehra, A., Burns, J., Liu, C. K., Manza, P., Wie= rs, C. E., Volkow, N. D., & Wang, G. J. (2018). Cannabis addiction and the bra= in: a review. Journal of Neuroimmune Pharmacology, 13, 438-452. https:/= /link.springer.com/article/10.1007/S11481-018-9782-9<= /span>

El artículo que se pub= lica es de exclusiva responsabilidad de los autores y no necesariamente reflejan= el pensamiento de la Revista Alfa Publicaciones.

El artículo queda en propiedad de la revist= a y, por tanto, su publicación parcial y/o total en otro medio tiene que = ser autorizado por el director de la R= evista Alfa Publicaciones.

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