Menopause symptoms and treatments | Benefits of cannabis for women’s health
November 20, 2021
Parkinson’s disease and cannabinoids Part II
December 10, 2021Scientific information for healthcare professionals
Author : Dr.Elmo Resende, Ph.D | Director of R&D - Piauhy Labs
Parkinson's disease treated with cannabinoids
Parkinson’s disease (PD) is a neurodegenerative brain disorder that affects the production of dopamine. PD symptoms appear progressively by manifesting less motor control and patients may experience tremors, stiffness, or balance difficulties. Alternative treatments have been studied as aim to avoid PD’s adverse effects, since modern drugs still cause some side reactions. Cannabinoids and endocannabinoid system present a positive connection in regulation of motor functions and antioxidant properties in PD.
Parkinson’s disease | Definition
Parkinson's disease (PD) is a degenerative disease of the central nervous system, it is a chronic and progressive disease. It is caused by an intense decrease in the production of dopamine, which is a neurotransmitter, that is, a chemical that helps transmit messages between nerve cells. PD was first described by James Parkinson in 1817.
Dopamine helps in performing voluntary body movements automatically, that is, we don't need to think about every movement our muscles perform throughout the day, thanks to the presence of this substance in our brains. In the absence of it, particularly in a small brain region called substantia nigra, the individual's motor control is lost, and this causes the characteristic signs and symptoms of this disease.
PD begins years before clinical diagnosis, involves several regions of the brain, and causes both motor and non-motor symptoms. It is a process of slow and progressive neurodegenerative disorder with a multifactorial etiology, resulting from a combination of genetic and environmental factors.
Parkinson’s disease | Common symptoms
PD causes tremors, muscle stiffness, difficulty walking, balance and motor coordination problems in general. PD symptoms usually start gradually and worsen over time. As the disease progresses, people with PD may find it difficult to walk and speak. These patients may also have mental and behavioral changes, sleep problems, depression, memory difficulties and fatigue.
PD is a degenerative disease of the central nervous system in which the substantia nigra cells in the midbrain gradually disappear and dopamine production progressivelly reduces. Midbrain damage can cause disruptions in the dopamine content of striated objects, a decrease in the density of dopamine receptors, a decrease in neuronal activity, and an increase in brain free radical activity. The degeneration of dopaminergic neurons in the midbrain and the marked decline of dopamine in the middle posterior part of the dense substantia nigra cause debilitating and motor disorders such as bradykinesia, resting tremor, rigidity, and postural instability.
Parkinson’s disease common motor symptoms | Tremor
PD is the most prevalent motor disease in the population and the second most prevalent neurodegenerative disorder in the entire world population, characterized by the progressive death of dopaminergic neurons, predominantly in the pars compact of the substantia nigra, in the neostriatum and in the nucleus subthalamic basal ganglia in small amounts.
It is known that the intracellular accumulation of Lewy bodies enriched in α-synuclein protein and protein inclusions, similar to threads called Lewy neuritis, provoke the motor symptoms present in this disease.
Patients affected by this disease have a history that consists of a gradual increase in tremors, greater slowness of movement, shuffling walking, leaning forward posture. The tremor affects the fingers or hands, but it can also affect the chin, head or feet. It can occur on one side of the body or in both, and it can be more intense on one side than on the other. Tremor occurs when no movement is being performed, which is why it is called resting tremor. This illness can also have a wide range of other physical and psychological symptoms such as depression and anxiety, balance problems (this can increase the chance of falling), loss of smell (anosmia), sleep problems (insomnia) and memory problems.
Parkinson’s disease | Traditional pharmacological treatments and side effects
Specific and traditional pharmacological therapy includes anti-dementia, which correspond to cholinesterase inhibitors. These drugs increase acetylcholine in the synaptic cleft, which is a neurotransmitter that is decreased in PD. In moderate or severe stages, the use of another class of drugs, memantine, alone or in association with cholinesterase inhibitors, may be considered.
The treatment of behavioral and psychological symptoms of dementia is essential and non-pharmacological or pharmacological interventions may be considered, namely the use of medications such as antidepressants, anxiolytics or psychotics.
Drugs that are cholinesterase inhibitors can have adverse effects, such as gastrointestinal, which are the most common, and include nausea, vomiting, diarrhea, anorexia, dyspepsia and abdominal pain; they also have cardiovascular effects, such as blood pressure fluctuation, syncope, arrhythmia and bradycardia, which is generally insignificant, but may destabilize patients with previous conduction defects, which justifies an electrocardiogram before starting the drug and, also, other symptoms in general, such as dizziness, headache, agitation, insomnia, cramps and sweating.
The most common side effects observed in patients who use nemantin medication are headache, constipation and dizziness.
For patients who use the drugs described as antidepressants, anxiolytics or antipsychotics, the most common adverse effects are tachycardia, sexual dysfunction and anticholinergic reactions. The most modern drugs, despite having greater tolerance, still have side reactions. The most common are gastrointestinal problems, headache, lack of motor coordination and changes in sleep, energy level, sedation, fatigue, memory loss, drowsiness, motor incoordination, decreased attention, concentration, reflexes, sedation, dizziness and weight gain.”
Dr. Resende
Parkinson’s disease and endocannabinoid system | Cannabinoids use in Parkinson disease treatment
The endocannabinoid system (ECS) modulates a wide range of physiological functions, including mood, cognition, motor control, eating behavior and pain. In recent years, a number of studies have explored the role of cannabinoids (CBs) in different pathological conditions.The ECS is highly represented in the basal ganglia and is altered in several movement disorders, including in PD. Preclinical research suggests that modulation of endocannabinoid signaling may improve motor symptoms.
The ECS activation was associated with motor inhibition and reduced dopaminergic activity. Classically, in hyperkinetic conditions, reduced endocannabinoid (eCB) tone accompanies increased dopaminergic activity, whereas in hypokinetic movement disorders, the opposite pattern is observed. In experimental models of PD, eCBs can increase the hypokinetic effects of disease-depleting agents and reduce the effects of drugs that produce hyperstimulation of disease receptors.
The eCBs are neurotransmitters derived from membrane phospholipids and are produced on demand by enzymes expressed throughout the central nervous system (CNS). The main endogenous ligands are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Simultaneously, the eCBs bind to cannabinoid receptors of subtypes 1 (CB1) and 2 (CB2).
Studies show that CB1 receptor agonists inhibit basal ganglia release in PD and are therefore expected to be ineffective in alleviating the motor symptoms of this disease. CB1 receptor agonists exacerbated bradykinesia at 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) – in injured primates.
However, different CB1 receptor agonists have also been reported to improve motor impairment, possibly through non-dopaminergic mechanisms, including interactions with adenosine A2A and 5-HT receptors.
THC benefits in Parkinson’s disease treatment
Components of the ECS are involved in the regulation of motor functions and dopamine activity. Therefore, cannabis appears to be a very attractive therapeutic option in the treatment of movement disorders and also neurodegenerative disorders. In fact, several studies have shown that medicinal Cannabis can help combat the motor symptoms of PD, such as stiffness, tremors and bradykinesia. In addition, it provides pain relief and reduces sleep disturbance in patients.
The various CBs have been extensively investigated over the last decades, in particular those that activate the CB2 receptor, which experiences an intense ascending regulatory response, predominantly in infiltrated microglial cells and macrophages, recruited from injured areas of the CNS, in patients with PD and in experimental animal models. Activation of this receptor in these experimental models has been associated with anti-inflammatory and neuroprotective effects.
Some more recent studies have proposed an alternative anti-inflammatory target for cannabinoids in this disease, the PPAR-γ receptor, which has been shown to play a relevant role in controlling inflammation in various pathological conditions.
THC is a phytocannabinoid (pCB) with affinity for CB1 and CB2 receptors, although its ability to protect dopaminergic neurons from death seems to be more related to its antioxidant properties than its ability to activate these types of receptors. This conclusion is also supported by the fact that equivalent neuroprotection was also achieved with Cannabidiol (CBD), an antioxidant pCB with negligible activity at both types of receptors.
Cannabinoids use in Parkinson’s disease treatment | CBD benefits in Parkinson’s disease treatment
The CB1 receptors are found primarily in the basal ganglia of the brain and in the CNS.
CBD is involved in reducing dopamine levels by activating or inhibiting CB1 and/or CB2 receptors, as mentioned before. Furthermore, the sedative activity of CBD has been investigated, with reports of increased quality of sleep and wakefulness recorded, depending on the dosage and route of administration.
Treatment with CBD for PD significantly reduced both psychotic and motor symptoms and there was no worsening of cognitive symptoms. With these preliminary results, it was found that CBD can have positive effects on PD. One of the first effects observed with the use of CBD was its sedative action, and thus it was found that patients with PD reported improved sleep quality, which is a common problem in this movement disorder.
Another important aspect that was observed in the use of CBD was the absence of fluctuation in psychiatric symptoms, that is, the common mood variation in those who use medications to control the non-motor symptoms of the disease, such as depression and anxiety, for example, that occur between intervals of medication use.
Overall, the role of the CB2 receptor is less explored than the role of the CB1 receptor, particularly with regard to innate immune responses in the acute state.
Activation of the CB2 receptor is associated with intracellular pathways that attenuate immune responses. Because of this, CB2 receptor agonists may hold promise as therapeutic agents in autoimmune diseases by suppressing antibody production through T cell mechanisms.
Several studies have shown that pCBs inhibit cytokine production in monocyte cell cultures and in animal models of acute infection, mainly through inhibition of induced activation of TLR4. This fact has also been demonstrated in humans who smoke Cannabis sativa, indicating that pCBs can impair TLR-induced immune activation.
The CBD exerts a variety of effects in laboratory animals and humans, including sedative/hypnotic, anticonvulsant, neuroprotective, cardiovascular, and anti-inflammatory effects. These actions do not appear to be dependent on cannabinoid receptors.
In a study involving the use of pCBs, daily administration of CBD (3 mg/kg) for 14 days decreased dopamine depletion and tyrosine hydroxylase expression in the striatum of rats receiving 6-hydroxydopamine (6-OHDA), which is an analogue to dopamine.
These neuroprotective effects were associated with an upregulation of mRNA levels of Cu2+/Zn su
peroxide dismutase, a key enzyme necessary for the endogenous control of oxidative stress.
“The mechanisms of action of CBD are still not fully understood. While THC acts as an agonist at cannabinoid receptors, CBD appears to have a more antagonistic effect and interacts with other neurotransmitter receptors such as serotonin, opioids and dopamine. It appears to act by decreasing the reuptake of anandamide, an eCB produced by humans.”
Dr. Resende
Cannabinoids use in Parkinson’s disease treatment | Piauhy’s Labs Mission
Piauhy Labs company, based in Portugal, aims to study the effect of cannabinoids on various diseases, including neurodegenerative diseases such as PD. In this sense, our will is the research with cannabinoids, terpenes and other components of the Cannabis sativa plant that may present positive results in combating PD, starting from in vitro studies, in animal models and, later, with our partners in Portugal and in other countries, carry out clinical studies. Our mission is also to bring out studies with monoclonal antibodies, targeting different diseases, such as neurodegenerative diseases such as PD.
Piauhy Labs intends to obtain a Certification of Compliance with Good Laboratory Practices, in accordance with the principles of the OECD, for the pharmaceutical area, so that the results obtained from its research are properly used for the granting of licenses or for the registration of pharmaceutical products, including medicines for human use and similar products.
As a result of the intended research processes, Piauhy Labs to create patents and originate intellectual property, with the ultimate goal of producing innovative medicines that improve the quality of life of patients suffering from various diseases, including Parkinson's disease.
References
Allenspach, M. and Steuer, C. α-Pinene: A never-ending story. Phytochemistry, volume 190, October, 112857, 2021.
Bassi, M. S.; Sancesario, A.; Morace, R.; Centonze, D. and Iezzi, E. Cannabinoids in Parkinson’s Disease. Cannabis and Cannabinoid Research, Volume 2.1, 2017.
Burgaz, S.; García, C.; Gómez-Cañas, M.; Muñoz, E. and Fernández-Ruiz, J. Development of An Oral Treatment with the PPAR-γ-Acting Cannabinoid VCE-003.2 Against the Inflammation-Driven Neuronal Deterioration in Experimental Parkinson’s Disease. Molecules 24, 2702, 2019.
Chagas, M. H. N.; Eckeli, A. L.; Zuardi, A., et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J. Clin. Pharm. Ther. Oct;39(5):564-6, 2014.
Chagas, M. H. N.; Zuardi, A. W.; Tumas, V. et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J. Psychopharmacol., Nov, 28 (11):1088-98, 2014.
Ferreira-Junior, N. C.; Campos, A. C.; Guimarães, F. S., Del-Bel, E.; Zimmermann, P. M. R.; Brum Junior, L., et al. Biological bases for a possible effect of cannabidiol in Parkinson’s disease. Braz. J. Psychiatr. 42 (2), Mar-Apr, 2020.
Goudarzi, S. and Rafieirad, M. Evaluating the effect of α-pinene on motor activity, avoidance memory and lipid peroxidation in animal model of Parkinson disease in adult male rats. Research Journal of Pharmacognosy (RJP) 4(2), 53-63, 2017.
Hickman, S.; Izzy, S.; Sen, P.; Morsett, L. and El Khoury, J. Microglia in neurodegeneration. Nature Neuroscience 21(10), 1359–1369, 2018.
Ingelsson, M. Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson’s Disease and Other Lewy Body Disorders. Front. Neurosci. 10:408, 2016.
Kaura, K.; Khuranaa, N. and Sharmaa, N. Phytochemicals as Future Drugs for Parkinson´s Disease: A Review. Plant Archives 21, Supplement 1, 2338-2349, 2021.
Kessler, F. H.; von Diemen, L.; Ornell, F. and Sordi, A. O. Cannabidiol and mental health: possibilities, uncertainties, and controversies for addiction treatment. Braz. J. Psychiatry May 17, 2021.
Pradeep Kumar, P.; Mahato, D. K.; Kamle, M.; Borah, R.; Sharma, B.; Pandhi, S.; Tripathi, V.; Yadav, H. S.; Devi, S.; Patil, U.; Xiao; J. and Mishra, A. K. Pharmacological properties, therapeutic potential, and legal status of Cannabis sativa L.: An overview. Phytother. Res. Jul 8, 2021.
Sexton, M. Cannabis in the Time of Coronavirus Disease 2019: The Yin and Yang of the Endocannabinoid System in Immunocompetence. The Journal of Alternative and Complementary Medicine, Volume 26, Number 6, 444–448, 2020.
Stasiłowicz, A.; Tomala, A.; Podolak, I. and Cielecka-Piontek, J. Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment. Int. J. Mol. Sci. 22, 778, 2021.
Parkinson's disease treated with cannabinoids
Parkinson’s disease (PD) is a neurodegenerative brain disorder that affects the production of dopamine. PD symptoms appear progressively by manifesting less motor control and patients may experience tremors, stiffness, or balance difficulties. Alternative treatments have been studied as aim to avoid PD’s adverse effects, since modern drugs still cause some side reactions. Cannabinoids and endocannabinoid system present a positive connection in regulation of motor functions and antioxidant properties in PD.
Parkinson’s disease | Definition
Parkinson's disease (PD) is a degenerative disease of the central nervous system, it is a chronic and progressive disease. It is caused by an intense decrease in the production of dopamine, which is a neurotransmitter, that is, a chemical that helps transmit messages between nerve cells. PD was first described by James Parkinson in 1817.
Dopamine helps in performing voluntary body movements automatically, that is, we don't need to think about every movement our muscles perform throughout the day, thanks to the presence of this substance in our brains. In the absence of it, particularly in a small brain region called substantia nigra, the individual's motor control is lost, and this causes the characteristic signs and symptoms of this disease.
PD begins years before clinical diagnosis, involves several regions of the brain, and causes both motor and non-motor symptoms. It is a process of slow and progressive neurodegenerative disorder with a multifactorial etiology, resulting from a combination of genetic and environmental factors.
Parkinson’s disease | Common symptoms
PD causes tremors, muscle stiffness, difficulty walking, balance and motor coordination problems in general. PD symptoms usually start gradually and worsen over time. As the disease progresses, people with PD may find it difficult to walk and speak. These patients may also have mental and behavioral changes, sleep problems, depression, memory difficulties and fatigue.
PD is a degenerative disease of the central nervous system in which the substantia nigra cells in the midbrain gradually disappear and dopamine production progressivelly reduces. Midbrain damage can cause disruptions in the dopamine content of striated objects, a decrease in the density of dopamine receptors, a decrease in neuronal activity, and an increase in brain free radical activity. The degeneration of dopaminergic neurons in the midbrain and the marked decline of dopamine in the middle posterior part of the dense substantia nigra cause debilitating and motor disorders such as bradykinesia, resting tremor, rigidity, and postural instability.
Parkinson’s disease common motor symptoms | Tremor
PD is the most prevalent motor disease in the population and the second most prevalent neurodegenerative disorder in the entire world population, characterized by the progressive death of dopaminergic neurons, predominantly in the pars compact of the substantia nigra, in the neostriatum and in the nucleus subthalamic basal ganglia in small amounts.
It is known that the intracellular accumulation of Lewy bodies enriched in α-synuclein protein and protein inclusions, similar to threads called Lewy neuritis, provoke the motor symptoms present in this disease.
Patients affected by this disease have a history that consists of a gradual increase in tremors, greater slowness of movement, shuffling walking, leaning forward posture. The tremor affects the fingers or hands, but it can also affect the chin, head or feet. It can occur on one side of the body or in both, and it can be more intense on one side than on the other. Tremor occurs when no movement is being performed, which is why it is called resting tremor. This illness can also have a wide range of other physical and psychological symptoms such as depression and anxiety, balance problems (this can increase the chance of falling), loss of smell (anosmia), sleep problems (insomnia) and memory problems.
Parkinson’s disease | Traditional pharmacological treatments and side effects
Specific and traditional pharmacological therapy includes anti-dementia, which correspond to cholinesterase inhibitors. These drugs increase acetylcholine in the synaptic cleft, which is a neurotransmitter that is decreased in PD. In moderate or severe stages, the use of another class of drugs, memantine, alone or in association with cholinesterase inhibitors, may be considered.
The treatment of behavioral and psychological symptoms of dementia is essential and non-pharmacological or pharmacological interventions may be considered, namely the use of medications such as antidepressants, anxiolytics or psychotics.
Drugs that are cholinesterase inhibitors can have adverse effects, such as gastrointestinal, which are the most common, and include nausea, vomiting, diarrhea, anorexia, dyspepsia and abdominal pain; they also have cardiovascular effects, such as blood pressure fluctuation, syncope, arrhythmia and bradycardia, which is generally insignificant, but may destabilize patients with previous conduction defects, which justifies an electrocardiogram before starting the drug and, also, other symptoms in general, such as dizziness, headache, agitation, insomnia, cramps and sweating.
The most common side effects observed in patients who use nemantin medication are headache, constipation and dizziness.
For patients who use the drugs described as antidepressants, anxiolytics or antipsychotics, the most common adverse effects are tachycardia, sexual dysfunction and anticholinergic reactions. The most modern drugs, despite having greater tolerance, still have side reactions. The most common are gastrointestinal problems, headache, lack of motor coordination and changes in sleep, energy level, sedation, fatigue, memory loss, drowsiness, motor incoordination, decreased attention, concentration, reflexes, sedation, dizziness and weight gain.”
Dr. Resende
Parkinson’s disease and endocannabinoid system | Cannabinoids use in Parkinson disease treatment
The endocannabinoid system (ECS) modulates a wide range of physiological functions, including mood, cognition, motor control, eating behavior and pain. In recent years, a number of studies have explored the role of cannabinoids (CBs) in different pathological conditions.
The ECS is highly represented in the basal ganglia and is altered in several movement disorders, including in PD. Preclinical research suggests that modulation of endocannabinoid signaling may improve motor symptoms.The ECS activation was associated with motor inhibition and reduced dopaminergic activity. Classically, in hyperkinetic conditions, reduced endocannabinoid (eCB) tone accompanies increased dopaminergic activity, whereas in hypokinetic movement disorders, the opposite pattern is observed. In experimental models of PD, eCBs can increase the hypokinetic effects of disease-depleting agents and reduce the effects of drugs that produce hyperstimulation of disease receptors.
The eCBs are neurotransmitters derived from membrane phospholipids and are produced on demand by enzymes expressed throughout the central nervous system (CNS). The main endogenous ligands are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Simultaneously, the eCBs bind to cannabinoid receptors of subtypes 1 (CB1) and 2 (CB2).
Studies show that CB1 receptor agonists inhibit basal ganglia release in PD and are therefore expected to be ineffective in alleviating the motor symptoms of this disease. CB1 receptor agonists exacerbated bradykinesia at 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) – in injured primates. However, different CB1 receptor agonists have also been reported to improve motor impairment, possibly through non-dopaminergic mechanisms, including interactions with adenosine A2A and 5-HT receptors.
THC benefits in Parkinson’s disease treatment
The various CBs have been extensively investigated over the last decades, in particular those that activate the CB2 receptor, which experiences an intense ascending regulatory response, predominantly in infiltrated microglial cells and macrophages, recruited from injured areas of the CNS, in patients with PD and in experimental animal models. Activation of this receptor in these experimental models has been associated with anti-inflammatory and neuroprotective effects. Some more recent studies have proposed an alternative anti-inflammatory target for cannabinoids in this disease, the PPAR-γ receptor, which has been shown to play a relevant role in controlling inflammation in various pathological conditions.
THC is a phytocannabinoid (pCB) with affinity for CB1 and CB2 receptors, although its ability to protect dopaminergic neurons from death seems to be more related to its antioxidant properties than its ability to activate these types of receptors. This conclusion is also supported by the fact that equivalent neuroprotection was also achieved with Cannabidiol (CBD), an antioxidant pCB with negligible activity at both types of receptors.
Cannabinoids use in Parkinson’s disease treatment | CBD benefits in Parkinson’s disease treatment
The CB1 receptors are found primarily in the basal ganglia of the brain and in the CNS.
CBD is involved in reducing dopamine levels by activating or inhibiting CB1 and/or CB2 receptors, as mentioned before. Furthermore, the sedative activity of CBD has been investigated, with reports of increased quality of sleep and wakefulness recorded, depending on the dosage and route of administration.
Treatment with CBD for PD significantly reduced both psychotic and motor symptoms and there was no worsening of cognitive symptoms. With these preliminary results, it was found that CBD can have positive effects on PD. One of the first effects observed with the use of CBD was its sedative action, and thus it was found that patients with PD reported improved sleep quality, which is a common problem in this movement disorder.
Another important aspect that was observed in the use of CBD was the absence of fluctuation in psychiatric symptoms, that is, the common mood variation in those who use medications to control the non-motor symptoms of the disease, such as depression and anxiety, for example, that occur between intervals of medication use.
Overall, the role of the CB2 receptor is less explored than the role of the CB1 receptor, particularly with regard to innate immune responses in the acute state.
Activation of the CB2 receptor is associated with intracellular pathways that attenuate immune responses. Because of this, CB2 receptor agonists may hold promise as therapeutic agents in autoimmune diseases by suppressing antibody production through T cell mechanisms.
Several studies have shown that pCBs inhibit cytokine production in monocyte cell cultures and in animal models of acute infection, mainly through inhibition of induced activation of TLR4. This fact has also been demonstrated in humans who smoke Cannabis sativa, indicating that pCBs can impair TLR-induced immune activation.
The CBD exerts a variety of effects in laboratory animals and humans, including sedative/hypnotic, anticonvulsant, neuroprotective, cardiovascular, and anti-inflammatory effects. These actions do not appear to be dependent on cannabinoid receptors.
In a study involving the use of pCBs, daily administration of CBD (3 mg/kg) for 14 days decreased dopamine depletion and tyrosine hydroxylase expression in the striatum of rats receiving 6-hydroxydopamine (6-OHDA), which is an analogue to dopamine.
These neuroprotective effects were associated with an upregulation of mRNA levels of Cu2+/Zn su
peroxide dismutase, a key enzyme necessary for the endogenous control of oxidative stress.
“The mechanisms of action of CBD are still not fully understood. While THC acts as an agonist at cannabinoid receptors, CBD appears to have a more antagonistic effect and interacts with other neurotransmitter receptors such as serotonin, opioids and dopamine. It appears to act by decreasing the reuptake of anandamide, an eCB produced by humans.”
Dr. Resende
Cannabinoids use in Parkinson’s disease treatment | Piauhy’s Labs Mission
Piauhy Labs company, based in Portugal, aims to study the effect of cannabinoids on various diseases, including neurodegenerative diseases such as PD. In this sense, our will is the research with cannabinoids, terpenes and other components of the Cannabis sativa plant that may present positive results in combating PD, starting from in vitro studies, in animal models and, later, with our partners in Portugal and in other countries, carry out clinical studies. Our mission is also to bring out studies with monoclonal antibodies, targeting different diseases, such as neurodegenerative diseases such as PD.
Piauhy Labs intends to obtain a Certification of Compliance with Good Laboratory Practices, in accordance with the principles of the OECD, for the pharmaceutical area, so that the results obtained from its research are properly used for the granting of licenses or for the registration of pharmaceutical products, including medicines for human use and similar products.
As a result of the intended research processes, Piauhy Labs to create patents and originate intellectual property, with the ultimate goal of producing innovative medicines that improve the quality of life of patients suffering from various diseases, including Parkinson's disease.
References
Allenspach, M. and Steuer, C. α-Pinene: A never-ending story. Phytochemistry, volume 190, October, 112857, 2021.
Bassi, M. S.; Sancesario, A.; Morace, R.; Centonze, D. and Iezzi, E. Cannabinoids in Parkinson’s Disease. Cannabis and Cannabinoid Research, Volume 2.1, 2017.
Burgaz, S.; García, C.; Gómez-Cañas, M.; Muñoz, E. and Fernández-Ruiz, J. Development of An Oral Treatment with the PPAR-γ-Acting Cannabinoid VCE-003.2 Against the Inflammation-Driven Neuronal Deterioration in Experimental Parkinson’s Disease. Molecules 24, 2702, 2019.
Chagas, M. H. N.; Eckeli, A. L.; Zuardi, A., et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson's disease patients: a case series. J. Clin. Pharm. Ther. Oct;39(5):564-6, 2014.
Chagas, M. H. N.; Zuardi, A. W.; Tumas, V. et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J. Psychopharmacol., Nov, 28 (11):1088-98, 2014.
Ferreira-Junior, N. C.; Campos, A. C.; Guimarães, F. S., Del-Bel, E.; Zimmermann, P. M. R.; Brum Junior, L., et al. Biological bases for a possible effect of cannabidiol in Parkinson’s disease. Braz. J. Psychiatr. 42 (2), Mar-Apr, 2020.
Goudarzi, S. and Rafieirad, M. Evaluating the effect of α-pinene on motor activity, avoidance memory and lipid peroxidation in animal model of Parkinson disease in adult male rats. Research Journal of Pharmacognosy (RJP) 4(2), 53-63, 2017.
Hickman, S.; Izzy, S.; Sen, P.; Morsett, L. and El Khoury, J. Microglia in neurodegeneration. Nature Neuroscience 21(10), 1359–1369, 2018.
Ingelsson, M. Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson’s Disease and Other Lewy Body Disorders. Front. Neurosci. 10:408, 2016.
Kaura, K.; Khuranaa, N. and Sharmaa, N. Phytochemicals as Future Drugs for Parkinson´s Disease: A Review. Plant Archives 21, Supplement 1, 2338-2349, 2021.
Kessler, F. H.; von Diemen, L.; Ornell, F. and Sordi, A. O. Cannabidiol and mental health: possibilities, uncertainties, and controversies for addiction treatment. Braz. J. Psychiatry May 17, 2021.
Pradeep Kumar, P.; Mahato, D. K.; Kamle, M.; Borah, R.; Sharma, B.; Pandhi, S.; Tripathi, V.; Yadav, H. S.; Devi, S.; Patil, U.; Xiao; J. and Mishra, A. K. Pharmacological properties, therapeutic potential, and legal status of Cannabis sativa L.: An overview. Phytother. Res. Jul 8, 2021.
Sexton, M. Cannabis in the Time of Coronavirus Disease 2019: The Yin and Yang of the Endocannabinoid System in Immunocompetence. The Journal of Alternative and Complementary Medicine, Volume 26, Number 6, 444–448, 2020.
Stasiłowicz, A.; Tomala, A.; Podolak, I. and Cielecka-Piontek, J. Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment. Int. J. Mol. Sci. 22, 778, 2021.
