ALS, also known as Amyotrophic Lateral Sclerosis or Lou Gehrig’s Disease, affects the motor neurons of the spinal cord, which causes progressive weakness and muscle atrophy.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative condition that leads to the loss of motor neurons and control over voluntary muscles. Its symptoms progress from muscle weakness and wasting to difficulties in movement, eating, speaking, and ultimately, breathing. On average, patients diagnosed with ALS survive for two to five years, but there are exceptions like Cathy Jordan, a cannabis activist, who has lived with the disease for over three decades. Patients often experience pain and cognitive issues.
The cause of ALS is largely unknown, but one theory suggests that in familial cases, a malfunction in the production of an antioxidant called superoxide dismutase 1 (SOD1) may result in nerve damage due to free radicals. Cannabinoids, known for their antioxidant properties, could be relevant in this context.
Another theory links ALS to excessive glutamate (a common brain neurotransmitter) causing excitotoxicity and cell death. The endocannabinoid system, which regulates glutamate, may play a role.
Early surveys showed that ALS patients using cannabis found relief from appetite loss, depression, pain, spasticity, and drooling, but it was less effective for speech, swallowing, or sexual problems. A real-world study involving 32 patients endorsed the use of a THC/CBD spray to control spasticity. Additionally, ALS patients' endocannabinoid levels seemed to correlate with their disease progression. Media reports and case studies emphasize the need for more clinical trials on ALS and cannabinoids.
In a mouse model of ALS:
Treatment with THC at the onset of tremors delayed motor impairment and prolonged survival. In spinal cell cultures, THC “was extremely effective at reducing oxidative damage” and reducing excitotoxicity
Best Review Articles:
2021: For amyotrophic lateral sclerosis (ALS – or Lou Gehrig’s disease), this review suggests targeting the CB2 receptor to delay the disease progression
Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis
2019: A meta-analysis of the ten preclinical studies of cannabinoids & ALS
Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: a systematic review and meta-analysis
2016: A review of ALS, the cannabinoids & the pathways they use
Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?
2008: A review of the ECS in ALS
The endocannabinoid system in amyotrophic lateral sclerosis
2021: In a mouse model of ALS, inactivating the CB2 receptor worsened the disease progression
Inactivation of the CB 2 receptor accelerated the neuropathological deterioration in TDP-43 transgenic mice, a model of amyotrophic lateral sclerosis
2020: In humans with ALS, their blood levels of AEA, 2-AG & 2-OG were predictive of their disease state (66 patients)
Endocannabinoids and related lipids in serum from patients with amyotrophic lateral sclerosis
2019: In humans with ALS, a combination of THC & CBD found helpful (32 patients in a retrospective mono-centric cohort study)
Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD)
2017: In a tissue model of ALS, CBD changed genes related to ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity
Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis
2017: A case study of using CBD for ALS
[Self-medication with cannabidiol oil in a patient with primary lateral sclerosis]
2014: in mouse model of ALS, help seen for ALS with Sativex (a 1:1 THC:CBD formulation) via upregulation of CB2
Changes in endocannabinoid receptors and enzymes in the spinal cord of SOD1(G93A) transgenic mice and evaluation of a Sativex(®) -like combination of phytocannabinoids: interest for future therapies in amyotrophic lateral sclerosis
2010: In a mouse model of ALS, CB1 receptors very sensitive for controlling glutamate and GABA levels
Abnormal sensitivity of cannabinoid CB1 receptors in the striatum of mice with experimental amyotrophic lateral sclerosis
2008: In a mouse model of ALS, evidence for changes in level of CB1 & AMPA receptors
Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity
2007: In a mouse model of ALS, CB2 agonist slowed degeneration and preserved motor function
The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset
2006: In human spinal cords, the glial cells activated in MS & ALS show more COX2, P2X7 & CB2 – agonists suggested as therapeutic
COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord
2006: In a mouse model of ALS, synthetic and genetic methods to increase endocannabinoid levels show help for ALS
Increasing cannabinoid levels by pharmacological and genetic manipulation delay disease progression in SOD1 mice
2006: In a mouse model of ALS, a synthetic CB1 agonist delays disease progress
AM1241, a cannabinoid CB2 receptor selective compound, delays disease progression in a mouse model of amyotrophic lateral sclerosis
2005: In a mouse model of ALS, CBN delayed disease onset
Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival
2004: In a mouse model of ALS, THC delayed motor impairment and prolonged survival as well as attenuating excitotoxic and oxidative cell damage
Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid
2004: A survey of 13 cannabis users found it might be helpful for ALS
Survey of cannabis use in patients with amyotrophic lateral sclerosis