MEDICAL CANNABIS RESEARCH BY TIKUN OLAM

Tikun Olam Medical Studies Overview

Medical Research

Tikun Olam is a proud pioneer and global leader in medical cannabis research. Rooted in Israel’s regulatory environment, our team of scientists have conducted cannabis studies and clinical trials for more than a decade, achieving outstanding results and amassing one of the world’s largest cannabis treatment databases of currently more than 20,000 patients.

Through extensive research and development, Tikun’s proprietary strains have been genetically optimized and clinically proven to provide symptomatic relief for a wide variety of ailments, including Crohn’s Disease, Parkinson’s Disease, autism, cancer, Inflammatory Bowel Disease, and more.

Clinical successes have encouraged Tikun to devote more resources to further improve the safety and efficacy of its products, as well as it’s understanding of the therapeutic properties of the cannabis plant. Tikun continually conduct laboratory studies (both in vitro and in vivo), retrospective analyses, and clinical trials, and works diligently to follow-up
with patients.

Below is an outline of medical cannabis research as of February 2022.

Completed & Published Research

1) Timna Naftali, et al. Treatment of Crohn's Disease with Cannabis: An Observational Study.

[The Israel Medical Association Journal, 2011;13(8):455-8]

This retrospective study observed cannabis as treatment for Crohn’s Disease and found that cannabis use resulted in significant positive effects on the symptoms of the disease (number of bowel movements, quality of bowel activity, abdominal pain, and other complications)

Study Population: 30 patients with Crohn’s Disease

Strain Used: Erez

Key Results:

• 21 of the 30 patients improved significantly with cannabis treatment

• The average Harvey Bradshaw Index improved from 14 ± 6.7 to 7 ± 4.7 (p<.00 1); the index measures general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and related complications

• The mean number of bowel movements decreased from 8 to 5 per day

• The need for other medication was significantly reduced; most notably, the number of patients needing steroid treatment reduced from 26 to 4

• Only 2 of 15 patients who had surgery prior to cannabis treatment needed additional surgery during treatment

• 18.1% of patients stopped using opioid analgesics or reduced their dose

2) Timna Naftali, et al. Cannabis Induces a Clinical Response in Patients with Crohn's Disease: A Randomized Placebo-Controlled, Double-Blind Study

[Clinical Gastroenterology & Hepatology 2013;11(10):1276-80]

In the world’s first randomized, placebo-controlled, double-blind study of its kind, Dr. Naftali and a team of researchers used Tikun Olam’s Erez strain to produce dramatic results, with 45% of Crohn’s patients achieving “complete remission” and over 90% achieving substantial improvement – with no side effects witnessed.
Study Population: 21 patients with Crohn’s Disease Activity Index (CDAI) scores greater than 200, who did not respond to therapy with steroids, immune-modulators, or anti-tumor agents; 11 of the patients were in the cannabis treatment study group, 10 were in the placebo control group.

Strain Used: Erez

Key Results:

Complete remission (CDAI score <150) was achieved by 5 of the 11 patients in the cannabis group
Clinical response (decrease in CDAI score of >100) was observed in 10 of the 11 patients
3 of the 11 patients were weaned from steroid dependency
The cannabis group reported significantly less pain, and improved appetite and quality of life.

3) Timna Naftali, et al. Oral CBD-rich Cannabis Induces Clinical but Not Endoscopic Response in Patients with Crohn's Disease, a Randomised Controlled Trial.

[Journal of Crohn’s and Colitis 2021;15(11):1799-1806]

Study participants underwent an eight-week follow-up in which each participant received Avidekel or placebo oil and an additional two weeks of wash-up to see what happens during consumption cessation, a total of ten weeks of follow-up.

During the study, patients attended four visits and were evaluated by medical interview, physical examination, blood and stool tests. In addition, a colonoscopy was performed before the start of cannabis treatment and at the end of eight weeks of treatment.

Study Population: 56 patients with Crohn’s disease (30 males, mean age 34.5).

Study Product: Avidekel oil with 16% CBD and 4% THC VS placebo (46% of patients received placebo).

Key Results:

No patient stopped treatment during the 10 weeks of follow-up.
Improvement in disease symptoms – The CDAI score (Crohn’s disease activity index) improved significantly in the cannabis group, compared to the improvement in the placebo group.
Decrease in abdominal pain – there was a significant relief in the intensity of abdominal pain in the cannabis group (decrease in the CDAI score in the pain section), compared to the placebo group, in which the intensity of pain remained at the same level.
Improvement in the quality of life – In the cannabis group, a significant improvement in the quality of life was observed (an increase in the SF-36 questionnaire score), compared with the placebo group whose quality of life remained at the same level.
Positive overall effect of treatment – Patients were asked to rate from 1 to 7, where 1 = great improvement, 7 = severe deterioration, various aspects of life. In the cannabis group, a significant improvement was observed in the various areas.
Side effects – No significant differences were observed between the cannabis group and the placebo group.

4) Timna Naftali, et al. Cannabis for Inflammatory Bowel Disease.

[Digestive Diseases 2014;32(4):468-74]

A retrospective study analyzing the effect CBD-enriched cannabis oil had on children and adolescents with refractory epilepsy, being treated at four epilepsy centers in Israel.

5) Timna Naftali, et al. Medical cannabis for inflammatory bowel disease: real-life experience of mode of consumption and assessment of side-effects.

[European Journal of Gastroenterology & Hepatology 2019;31(11):1376-1381]

Inflammatory bowel diseases (mainly Crohn’s and colitis) are chronic, debilitating, non-infectious, inflammatory diseases of the digestive tract. Conventional treatment consists of anti-inflammatory and immunomodulating drugs. However, the rate of response to currently available treatments is limited to 40–60%, and many patients remain symptomatic despite maximal medical treatment. This study, conducted in collaboration with the Gastroenterology Unit at Meir Medical Center, is a large-scale, long-term study that included data on patients licensed to treat medical cannabis with inflammatory bowel disease to determine the effect of cannabis on disease symptoms on long-term treatment as well as side effects. Most patients reported significant improvement in their symptoms and the use of other medications after 1 year of cannabis consumption was significantly reduced.

Study Population: 127 Crohn’s and colitis patients who received a license for use of medical cannabis (86 males, mean age 39.6)

Strain Used: Half of the patients in the study received the company’s products regularly.

Key Results:

During the study period, 127 patients received a license to use medical cannabis and entered the study.

General improvement – the average Harvey-Bradshaw index, which measures the severity of the disease, improved from 14.0 to 7.0 (P <0.001).
Weight gain – During follow-up of 3.6 years (median 44 months), there was a slight but statistically significant weight gain of 2 kg.
Decrease in drug consumption – the need for other medications was significantly reduced.
Improve in employment rates – employment among patients increased from 65% to 74%.
From the study it can be concluded that most Crohn’s and colitis patients using cannabis are satisfied with a dose of 30 gram per month.
No negative effects of cannabis use were observed on the patients’ social or occupational status.
The side effects described by the patients were mild. The most common were dry mouth (63%), memory decline (34%), eye irritation (14%), dizziness, (13%) confusion (9%), and restlessness (8%).

6) Ruth Gallily, et al. Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol.

[Pharmacology & Pharmacy 2015;6(2):75-85]

This laboratory study was conducted on rodents to examine the effect of full-plant cannabis extract on inflammation and pain, in comparison with isolated CBD and commercial anti-inflammatory and anti-nociceptive drugs. Isolated CBD has been shown to have a bell-shaped dose-response, where healing is only observed within a very limited dose range, with no additional beneficial effect achieved at lower or higher doses. This trait of purified CBD poses challenges to clinical use; thus, this study aimed to find a CBD source that eliminates the bell-shaped dose response – and succeeded with Avidekel.

Study Population: Lab mice

Strain Used: Avidekel

Key Results:

The full-plant extract of Avidekel. which is high in CBD and low in THC, provided a correlative antiinflammatory and anti-pain dose-response (i.e. as the dose was increased, the pain and inflammation decreased in correlation), superior to the bell-shaped dose-response of isolated CBD, which exhibited less consistent antiinflammatory and anti-pain properties at lower and higher doses

Avidekel extract exhibited superior anti-inflammatory effectiveness compared to tramadol (an opioid analgesic) and aspirin (a non-steroid anti-inflammatory)

7) Michal Tzadok, et al. CBD-enriched Medical Cannabis for Intractable Pediatric Epilepsy.

[Seizure 2016;35:41-44]

A retrospective study analyzing the effect CBD-enriched cannabis oil had on children and adolescents with refractory epilepsy, being treated at four epilepsy centers in Israel.

Study Population: 74 children with intractable epilepsy (between the ages of 1-18, half of them under the age of 10) with intractable epilepsy, resistant to 5-7 antiepileptic drugs

Strains used: About half of the patients in the study received the company’s products regularly

(CBD-enriched, mostly Avidekel 30%).

Key Results:

5 (6.7%) children discontinued treatment during 10 months of follow-up.

Overall improvement – CBD treatment had a positive and significant effect on the frequency and intensity of seizures.
Decrease in seizures – Most of the children (66/74, 89%) reported reduction in seizure frequency: 13 (18%) reported 75–100% reduction, 25 (34%) reported 50–75% reduction, 9 (12%) reported 25–50% reduction, and 19 (26%) reported <25% reduction. Five (7%) patients reported aggravation of seizures which led to CBD withdrawal.

Improvement in various aspects – there improvement in behavior and alertness, language, communication, motor skills and sleep.

Side effects included somnolence, fatigue, gastrointestinal disturbances and irritability leading to withdrawal of cannabis use in 5 patients.

8) Yacov Balash, et al. Medical Cannabis in Parkinson's Disease.

[Clinical Pharmacology 2017;40(6):268-272]

A retrospective questionnaire-based survey that examined the eects of cannabis on the motor and non-motor symptoms of patients with Parkinson’s Disease. The mean age of the patients was 64.2 ± 10.8 years, the mean disease duration was 10.8 ± 8.3 years, and the duration of cannabis use was 19.l ± 17 months.

Study Population: 47 patients with Parkinson’s Disease

Strains used: Various medical cannabis strainsp

Key Results:

82.2% of patients reported that cannabis improved their overall symptoms
81.4% of patients reported that their pain was reduced
76.1% of patients reported an improvement in mood
73.2% of patients reported tremor reduction
72.7% of patients reported reduced muscle stiffness
71.1% of patients reported an improvement in sleep quality

9) Ran Abuhasira, et al. Epidemiological Characteristics, Safety and Efficacy of Medical Cannabis in The Elderly.

[European Journal of Internal Medicine 2018;49:44-50 ]

A prospective study that analyzed the use of cannabis treatment in the elderly, measuring for pain intensity, quality of life, and adverse effects at six months follow-up. The most common indications for cannabis treatment were pain (66.6%) and cancer (60.8%). The study found that the therapeutic use of cannabis is safe and efficacious in the elderly population.

Study Population: 2,736 patients aged 65+; at 6 months, 901 patients were eligible for follow-up and completed the survey

Strains used: Erez. Alaska. Avidekel

Key Results:

93.73 of patients reported that the cannabis treatment improved their condition
Reported pain significantly reduced from a median of 8/10 to 4/10
Prior to treatment, 66.8% of patients reported high pain-intensity; at six months, this number decreased to only 7.6% of patients

35.1% of patients reported a decrease in the number of drugs taken or the dosage

18.1% stopped using opioid analgesics or reduced their dose
The most common reported side effects were dizziness (9.7%) and dry mouth (7.1%)

10) Lihi Bar-Lev Schleider, et al. Prospective Analysis of Safety and Efficacy of Medical Cannabis in Large Unselected Population of Patients with Cancer.

[European Journal of Internal Medicine 2018;49:37-43]

A study analyzing the data routinely collected as part of the treatment program of cancer patients treated with medical cannabis between 2015 and 2017. The cancer types included breast (20.7%), lung (13.6%), pancreatic (8.1%) and colorectal (7.9%); with 51.2% of patients at Stage 4. The main symptoms requiring therapy were sleep problems (78.4%), pain (77.7%; median intensity 8/10), weakness (72.7%), nausea (64.6%) and lack of appetite (48.9%).

Study Population:2,970 cancer patients; after six months of treatment, 1,211 patients were eligible for follow-up and responded to the questionnaire

Strain Used: Midnight, Avidekel, and other THC-rich Tikun Olam strains

Key Results:

95.9% of patients reported an improvement in their condition
Prior to treatment, 52.9% of patients reported their pain in the 8-10 interval; after six months, only 4.6% of patients reported this intensity

Prior to treatment, only 18.7% of patients reported “good” quality of life; after six months, 69.5% of patients reported “good” quality of life

The most improved symptoms were nausea and vomiting (91%), sleep disorders (87.5%), restlessness (87.5%), anxiety and depression (84.2%), pruritus (82.1%) and headaches (81.4%)
35.1% of patients decreased their drug consumption, including analgesics, sedatives, corticosteroids, and opioids
At intake, 344 patients used opioids; after six months, 36% stopped taking opioids and 9.9% reduced their dose
The most common side effects reported were dizziness (8%) and dry mouth (7.3%).

11) Stephanie Libzon, et al. Medical Cannabis for Pediatric Moderate to Severe Complex Motor Disorders.

[Journal of Child Neurology 2018;33(9):565-571]

A clinical random trial examining the effects of Avidekel oil on dystonia and spasticity in children who sufer from cerebral palsy or genetic impairment. Most participants reported significant improvement in spasticity and dystonia, sleep difficulties, pain severity, and quality of life.

Study Population: 20 patients with complex motor disorders (primarily cerebral palsy)

Strains used: Avidekel. Tested at 6:1 and 20:1 CBD:THC ratiosp

Key Results:

CBD-enriched 5% cannabis oil with CBD:THC ratios of 6:1 and 20:1 are effective in reducing the severity of dystonia and spasticity, and improving motor function ability and quality of life
All patients demonstrated mood and appetite improvement
Patients treated with the 6:1 ratio oil demonstrated sleep improvement
Patients treated with the 20:1 ratio oil demonstrated improvement in constipation

12) Ruth Gallily and Zhannah Yekhtin. Avidekel Cannabis Extracts and Cannabidiol are as Efficient as Copaxone in Suppressing EAE in SJL/J Mice.

[Inflammopharmacology 2019;27(1):167-173]

A study comparing the efficacy of purified CBD, extracts of CBD-rich Avidekel and Copaxone (glatiramer acetate), an immunosuppressive medication that is used to alleviate the symptoms of multiple sclerosis (MS).

Study Population: Lab mice

Strains used: Avidekel

Key Results:

CBD and Avidekel extracts are as efficient as Copaxone in alleviating the symptoms of EAE (animal model of brain inflammation) in lab mice; thus,

Avidekel may be useful in the treatment of MS symptoms

13) Avner Thaler, et al. Single Center Experience with Medical Cannabis in Gilles de la Tourette Syndrome.

[Parkinsonism and Related Disorders 2019;61:211-13]

A study conducted to assess the response and benefits of using cannabis to treat Tourette Syndrome.

Study Population: 42 patients with Tourette Syndrome

Strains used: Erez

Key Results:

The mean ranking of efficacy was 3.85 out of 5, indicating a positive response to medical cannabis

Patients reported reduction in tic severity, better sleep, and improved mood

14) Adi Aran, et al. Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems - A Retrospective Feasibility Study.

[Journal of Autism and Developmental Disorders 2019;49(3):1284-1288]

A retrospective study assessing the tolerability and ecacy of CBD-rich cannabis in children with ASD.

Study Population: 60 children with ASD and severe behavioral problems

Strains used: Avidekel, at a 20:1 CBD:THC ratio

Key Results:

Considerable improvement was reported in behavior (61%), communication (47%), and anxiety (39%),

after at least 3 months of cannabis treatment

33% of children reduced their other medication doses and 24% stopped taking medications altogether

15) Lihi Bar-Lev Schleider, et al. Real Life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy.

[Scientific Reports 2019;9(1):200]

An observational study assessing the safety and efficacy of medical cannabis for the treatment of autism spectrum disorders (ASD), analyzing the change in symptoms after six months of using our CBD-rich Avidekel cannabis oil.

Study Population: 188 children with ASD; 93 completed the follow-up survey at six months

Strains used: Avidekel, at a 20:1 CBD:THC ratio

Key Results:

90.2% of patients reported an improvement in symptoms after six months treatment
Symptoms improved included depression (100%), restlessness (89.8%), rage attacks (89%), anxiety (88.8%), seizures (84.6%), agitation (83.8%), tics (80%), digestion problems (62.5%), constipation (62.5%), sleep problems (58.6%), and more

“Good” quality of life was indicated by 31.1% of patients at intake; by 66.8% at six months
34.3% of patients decreased medication consumption, including antipsychotics, antiepileptics, antidepressants, hypnotics, and sedatives

20% of patients stopped taking antipsychotics
Cannabis appears to be a well-tolerated, safe, and effective option to relieve ASD symptoms

16) Dana Barchel, et al. Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities.

[Frontiers in Pharmacology 2019;9:1521]

Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. The aim of this study, conducted in collaboration with the Clinical Pharmacology and Toxicology Unit at Assaf Harofeh Medical Center, was to examine prospectively the safety characteristics and the changes in symptoms by a bi-weekly questionnaire. Parents’ reports suggest that cannabidiol may improve ASD comorbidity symptoms.

Study Population: 53 children diagnosed with ASD (45 boys, mean age 11).

Strain Used: Avidekel 20:1 30% CBD and Erez 3% THC extracts.

Key Results:

2 patients (3.7%) discontinued treatment during the study (lasting 66 days on average) and another 2 patients continued cannabis treatment with another provider.

Overall improvement – An improvement in ASD symptoms was reported in 74.5% of patients.
Decreased self-injury and rage attacks – Self-injury and rage attacks improved in 67.6% of patients.
Decreased hyperactivity – Hyperactivity symptoms improved in 68.4%.
Improved sleep – Sleep problems improved in 71.4%.
Decreased anxiety – Anxiety improved in 47.1%.
Side effects included drowsiness, decreased appetite, and increased appetite

17) Iftach Sagy, et al. Safety and efficacy of Medical Cannabis in Fibromyalgia.

[Journal of Clinical Medicine 2019;8(6):807]

Study Population: 53 children diagnosed with ASD (45 boys, mean age 11).

Strain Used: Avidekel 20:1 30% CBD and Erez 3% THC extracts.

Key Results:

81.1% of patients reported overall treatment success – defined as experiencing at least moderate improvement in their condition without serious adverse events
73,4% of patients reported improved sleep; 13.2% reported their sleeps problems were fully relieved
80.8% of patients reported improved-related symptoms
61.9% of patients reported their quality of life (QoL) to be “good or very good”, whereas only 2.7% of patients rated their QoL at this level prior to beginning treatment; QoL components include appetite, sleep quality, and sexual activity
Overall pain intensity reduced from a median of 9/10 at baseline to 5/10 after six months
22.2% of patients stopped or reduced their dosage of opioids; 20.3% reduced their dosage of benzodiazepines

18) Timna Naftali, et al. Placebo-controlled study - Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial.

[PLoS One 2021;16(2):e0246871]

Ulcerative colitis is an inflammatory bowel disease characterized by inflammation of the large intestine. The disease poses a significant personal and socioeconomic burden due to its effects on patients’ quality of life, daily functioning and use of healthcare system. The most common symptoms in colitis patients are: multiple bowel movements, severe abdominal pain and blood in the stool. The current treatment carries many long-term risks including malignancies, infections, and decreased bone density. Therefore, it is not surprising that many patients with colitis seek alternative treatments for their illnesses. A common such alternative treatment is the use of cannabis. However, clinical studies in the field are lacking. The aim of this randomized, double-blind, placebo-controlled study, conducted in collaboration with Meir Medical Center, was to evaluate the effect of medical cannabis on the clinical condition of ulcerative colitis patients. Cannabis treatment induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis.

Study Population: 32 patients with ulcerative colitis (18 males, mean age 30).

Study Product: Erez rolls compared to placebo (47% of patients received placebo).

Key Results:

No patient stopped treatment during the 8 weeks of follow-up. 17 patients (53%) continued treatment for another year after the study ended.
Overall improvement – a clinical response (considered to be above 3 points in the Lichtiger index score) was observed in the cannabis group more significantly than in the placebo group; Cannabis group patients improved from 10.9 to 5.0. There was also a decrease in the score of the placebo group, due to the placebo effect, but was more moderate from 11.0 to 8.0.
Decrease in the number of bowel movements per day – In the cannabis group, the number of bowel movements per day decreased from 2.6 to 1.0. In the placebo group, the number of bowel movements decreased from 2.6 to 2.
Decrease in abdominal pain – of the patients who reported severity of abdominal pain of ≥2 (on a scale of 1 to 10, with 10 being the highest level of pain), in the cannabis group the level of pain decreased from 10 to 1. In the placebo group, the level of pain decreased from 9 to 8.

Improvement in quality of life – The cannabis group observed a significant improvement in quality of life (from a score of 77 to a score of 98), compared to the placebo group whose quality of life remained at the same level (score of 78 all the way).

Symptomatic improvement – The cannabis group patients reported a significant improvement compared to the placebo group also in appetite, concentration, libido, pain, general satisfaction with the treatment (on a grade from 1 to 7, 1 = improved, 4 = no change, 7=deteriorated).
Side effects – No significant differences were observed between the cannabis group and the placebo group.

19) Lihi Bar-Lev Schleider, et al. Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological characteristics of the Patient Population: A prospective Study.

[Frontiers in Medicine 2022;9(Article 827849)]

A prospective study investigating the adherence, safety, and effectiveness of patients to medical cannabis.

Study Population: ~10.000 patients with cancer (49.1%), non-specific pain (29.3%) etc

Strains used: Erez, Alaska, Avidekel

Key Results:

70.6% of patients experienced treatment success
91.5% of patients reported rage attacks decrease
89.5% of patients reported restlessness decrease
89.1% of patients reported improved sleep
88.9% of patients reported nausea improvement
Supervised medical-cannabis treatment is associated with high adherence, improvement in quality of life, and a decrease in pain level with a low incidence of serious adverse events