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Ethnopharmacological study of psychotic effects of moroccan plants.

Ethnopharmacological study of psychotic effects of Moroccan plants.

Cannabis for Schizophrenia: Trigger or Treatment?

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Zineb Ibn Lahmar Andaloussi1, Zouhra Doukkali2, katim Alaoui2, Khalid Taghzouti1.

1 Physiology and Physiopathology Team, Department of Biology – Faculty of Sciences, MOHAMMED V UNIVERSITY IN RABAT

2 Pharmacodynamy Research Team, ERP, Laboratory of Pharmacology and Toxicology, Faculty of Medicine and Pharmacy, MOHAMMED V UNIVERSITY IN RABAT, Morocco

Abstract

Background:

The relationship between cannabis and schizophrenia is rife with taboo; an ethnopharmacological survey was carried out in Morocco in order to identify the plants used in traditional Moroccan medicine in treatment of Schizophrenia specifically the use of cannabis sativa in this trouble.

Methods:

Twenty (20) herbalists were interviewed individually and each delivered the plants used to combat schizophrenia, Twenty Five (25) medicinal species spread. Over 18 families have been reported and identified. Statistical analysis of data from ethnobotanical investigation has inventory the cannabis is one of plants that can treat symptoms of schizophrenia.

Results:

The analysis of use of these plants indicats that the leaves and flowers are the most used parts successively (50%, 45%).

About 46% of moroccan herbalist are for using the cannabis as treatment and 18% of them cited the need for more biological analysis and tries clinics before admit this plant as much as healthy and effective treatment.

Conclusions:

Most of herbalists interviewed in this study with the new researches accord that Cannabis could be a beneficial addition to the treatment of psychiatric disorders. But it has been linked for decades to the onset of psychosis.

Key Word: Cannabis, Psychotic effect, Schizophrenia, Ethnobotany and Ethnopharmacology study, Treatment

Introduction

Cannabis sativa L., an annual herbaceous plant that is currently accepted as belonging to a family (Cannabinaceae) that has only one genus (Cannabis) with only one species (sativa) that is highly variable [1]. In the last few years, there has been a boost in the use of cannabis for medicinal purposes. This plant (Cannabis sativa L.) has a long history as herbal medicine, and a large variety of biological activities have been described [2]. Most important among these are the cannabinoids [3], which are unique to the cannabis plant. Several historic reviews have been written on Cannabis use as a therapeutic drug [4, 5- 6]. It is often consumed in its herbal form, using unconventional modes of intake such as smoking, vaporizing, tea or brownies [7]. The tea is attributed various therapeutic and prophylactic qualities and is used as a remedy for fever, cold and stress. Often these products are associated with health. Although it is legally not permitted, positive drug tests for cannabis use as well as intoxication have been reported after ingestion of such products [8]. Although widely seen as a potential trigger for schizophrenia, Cannabis Sativa also contains an ingredient that appears to have antipsychotic effects. Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties and as an Adjunctive Therapy in Schizophrenia [9].

Schizophrenia is a severe mental disorder in which people interpret reality abnormally. Schizophrenia may result in some combination of hallucinations, delusions, and extremely disordered thinking and behavior that impairs daily functioning, and can be disabling. World Health Organization (WHO) is promoting the use of traditional herbal treatments [10] and it is with this in mind that we are interested in the anti-schozophrenia herbal medicine practiced in Morocco.

This study provides an inventory of numerous plant species used as traditional remedies for psychose specifically schizophrenia in Morocco. We have highlighted botanical remedies which are promising sources of new compounds comprised of flavonoids, bioflavanones, xanthones, terpenoids, sterols and glycosides as well as compound formulas and supplements for future use in multimodal treatment approaches.

The advancement of plant therapies and their derivative compounds will require the identification and validation of compounds having specific anti-psychotic effects. In particular, there is need for the identification of the presence of compounds that affect dopamine, GABA, glutamate, TRP, opioid and cannabinoid receptors, serotonergic and chloride channel systems through bioactivity-guided, high-throughput screening and biotesting. This will create new frontiers for obtaining novel compounds and herbal supplements to relieve pain, stress anxiety and psychotic disorders.

The goal is to provide a broader outlook, which is needed to form the basis for selecting species for biotesting and the development of effective medications for indigenous use, and the integration as adjunctive therapy. The list highlights plants with potential for new medications that can be used to improve the treatment outcome and quality of life for patients suffering from psychotic disorders and the accompanying pains. Most medicinal plants are used to treat more than one disease or disease symptoms; therefore, it’s possible that this wealth of herb and plant species can be exploited for novel therapies against stress, anxiety, depression and neurological disorders.

[image: https://upload.wikimedia.org/wikipedia/commons/2/23/Marijuana-Cannabis-Weed-Bud-Gram.jpg]

Fig1: Dried cannabis bud can be used for medical therapy.

Methods

Description of the study

The information was obtained from the knowledge and know-how of more than 20 Moroccan herbalists. This study was conducted throughout the Moroccan territory and is based on an ethnobotanical survey sheet submitted to the respondents during individual interviews. The taxonomic identification of the species was carried out by botanists from the Scientific Institute of Mohammed V-Agdal University in Rabat, and with the help of botanical descriptions from the literature. The surveyed herbalists represent all regions of Morocco, Arabic and Berber. Ethnobotanical information recorded on raw data sheets was transferred to a database and then processed and analyzed.

Interviews with the traditional healers

Conversations with the healers were used to obtain information on the use of the plants can treat the symptoms of schizophrenia. The data collected for each plant include the vernacular name, the part used and the method of preparation of the remedy. During each discussion, we collected information about the practitioner himself and the medicinal plants recommended for the treatment of schizophrenia. Thus, the profile of each respondent includes his age, his level of education, his city, and his training.

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Results

Medicinal species used

On the indication of the phytotherapists, 26 plant species have been identified (Table 1), the frequency of use of these plants, allowed us to list plants selected as priority (Fig. 2). The species Cannabis sativa and Melissa were reported by 5 herbalists, followed by Lippia citriodora (4), Origanum, valeriana and crataegus (3)

Table 1

medicinal plants used by Moroccan herbalists in the treatment of psychoses

Botanical family Name

scientific Name

English Name

Frequency of use

Apiaceae

Ammodaucus leucotrichus

wooly cumin

1

Foeniculum vulgare

Sesamum indica

2

Pimpinella anisum

Anise

1

Astéraceae

Chamomilla nobilis

Chamomile

2

Cannabaceae

Cannabis sativa L.

Cannabis

5

Euphorbiaceae

Mercurialis annua

Mercuriale

2

Illiciaceae

Illicium verum

star anise

1

Lamiaceae

Lavandula officinalis

lavender

2

Melissa officinalis

Melissa

5

Origanum majorana

Marjoram

3

Rosmarinus officinalis

Rosemary

1

Salvia officinalis

Sage

1

Malvaceae

Hibiscus esculens

Hibiscus

1

Myrtaceae

Syzygium aromaticum

cloves

1

Myrtaceaeisticaceae

Myristica Fragrans

nutmeg

1

Papaveraceae

Papaver rhoeas

Red poppy

1

Papaver somniferum

Poppy plant

1

Passifloraceae

Passiflora incarnata

passiflora

2

Rosaceae

Crataegus monogyna

hawthorn

3

Rutaceae

Citrus aurantium.L

orange blossom

1

Tiliaceae

Tilia cordata

linden

1

Thymelaeaceae

Thymelaea hirsuta

Hairy Thymelaea

1

Urticaceae

Urtica urens

nettle

1

Valerianaceae

Valeriana officinalis

valerian

3

Verbenaceae

Lippia citriodora

verbena

4

Viscaceae

Viscum album

mistletoe

1

Fig. 2 The most common antipsychotic plants used

Botanical families used

Fig.3 the most botanical family used against schizophrenia in Moroccan traditional medicine

Of the 19 families surveyed, the most used are Lamiaceae represented by 5 species, Cannabaceae represented by Cannabis sativa followed by Apiaceae, Verbenaceae and Rosaceae (Fig. 3). Lamiaceae in Morocco is an important botanical family that includes about 226 species growing in Morocco [11]. In our sample 5 species are cited by herbalists as antipsychotics. This family is above all an important source of essential oils, phenols and flavonoids [12]. Cannabaceae include 1specie growing in Morocco [11].

Part used

The ethnobotanical survey revealed that the leaves are the most used parts with a percentage of 50% (Fig. 4), followed by flowers (45%), seeds (40%). The use of leaves can be explained by the fact that they are quickly harvested and easy to use [13].

Fig. 4 plant parts used

Method of preparation

Users are always looking for the easiest method to prepare the plants. Infusion and capsule are the most common methods of preparation (63%) (Fig.5).

Fig. 5 the most efficient ways of using According Herbalists: Inf: Infusion, Tab: Tablet, E.O: Essential oils, H.T: Herbal Tea

Medicinal Uses of Cannabis

Cannabis as traitement:

During the discussion with the herbalists interviewed, cannabis was proposed in treatment of these psychotic disorders, and the results obtained are shown schematically below.

Fig. 6 Medicinal Uses of Cannabis

36% of the herbalists surveyed were against this proposal (36%), the 2nd largest (46%) was for its use and the small part (18%) cited the need for several biological analyzes and clinical trials before to admit this plant as well as a healthy and effective treatment.

Region of belonging:

In Morocco, herbalists are spread all over the territory; according to our survey, herbalists in the Casablanca region are the most represented by 25% of the sample, followed by Agadir (20%), Temara (15%) and Oujda (10%) (Fig. 7).

Fig. 7 Distribution of herbalists by province

Experience:

35% of the 20 herbalists interviewed have been performing their duties since at least a decade, which sheds light on the expertise and originality of knowledge about the use of medicinal plants (Fig. 8).

Fig. 8 Year-round experience of herbalists

Level of study:

100% of the surveyed herbalists know how to read and write. 20% have the baccalaureate degrees and 25% have a primary level of study. Each of them has at least one book of traditional medicine and all live exclusively from their profession (Fig. 9).

Fig. 9 Level of study of herbalists

Discussion

The aim of this work was to promote traditional Moroccan healers and to seek in their knowledge and know-how medicinal plants with anti- schizophrenia properties, without any significant side effects (Table 1).

The analysis of the results obtained by this ethnobotanical survey allowed us to identify about twenty plants mainly used in Morocco to treat the manifestations of Schizophrenia (Fig. 2) Cannabis sativa and Melissa officinalis are the most used in this context.

Schizophrenia is a complex, chronic mental health disorder characterized by an array of symptoms. Abnormalities in neurotransmission have provided the basis for theories on the pathophysiology of schizophrenia, either an excess or a deficiency of neurotransmitters, including dopamine, serotonin, and glutamate. Also aspartate, glycine, and gamma aminobutyric acid (GABA) as part of the neurochemical imbalance of schizophrenia [14]. Both nonpharmacological and pharmacological treatments must be used to optimize long-term outcomes [15]. Pharmacotherapy is the mainstay of schizophrenia management. The adverse effects of schizophrenia medications can involve several organ systems.

Antipsychotic drugs comprise three main categories:1) typical, or traditional, antipsychotics, which are associated with high dopamine (D2) antagonism and low serotonin (5-HT2A) antagonism; 2) atypical antipsychotics that have moderate-to-high D2 antagonism and high 5-HT2A antagonism; and 3) atypical antipsychotics that demonstrated low D2 antagonism and high 5-HT 2A antagonism [15, 16, 17].

The use of cannabis sativa as medicine has not been rigorously tested due to production restrictions and other governmental regulations [18]. The Cannabis plant has a history of medicinal use dating back thousands of years across many cultures [19]. Interest in the medicinal uses of this plant has, however, increased in the last decades.

A number of medical organizations have requested removal of cannabis from the list of Schedule I controlled substances, followed by regulatory and scientific review. [20, 21] Others such as the American Academy of Pediatrics oppose the legalization of medical cannabis. [22]

Medical cannabis can be administered using a variety of methods, including liquid tinctures, vaporizing or smoking dried buds, eating cannabis edibles, taking capsules, using lozenges, dermal patches, or oral/dermal sprays and recreational use of this plant is illegal in most parts of the world, but its medical use of is legal in a number of countries.

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A Cannabis plant includes more than 400 different chemicals, of which about 70 are cannabinoids [23]. The number of active chemicals in cannabis is one reason why treatment with cannabis is difficult to classify and study [23]. The most psychoactive cannabinoid found in the cannabis plant is tetrahydrocannabinol (or delta-9-tetrahydrocannabinol, commonly known as THC). [19].Other cannabinoids include delta-8-tetrahydrocannabinol, cannabidiol (CBD), cannabinol (CBN), cannabicyclol (CBL), cannabichromene (CBC) and cannabigerol (CBG); they have less psychotropic effects than THC, but may play a role in the overall effect of cannabis. [19]. The most studied are THC, CBD and CBN [24].

A 2014 review stated that the variations in ratio of CBD-to-THC in botanical and pharmaceutical preparations determines the therapeutic against psychoactive effects (CBD attenuates THC’s psychoactive effects [25] of cannabis products [ 26] cannabinoids have also been recommended for anorexia, arthritis, migraine, and glaucoma

[27] There is tentative evidence that medical cannabis is effective at reducing posttraumatic stress disorder symptoms, but, as of 2015, there is insufficient evidence to confirm its effectiveness for this condition.[28]

A major concern with the medicinal use of cannabis is the risk of (accidental) overdosing of THC, which could lead to psychotropic effects. Long-term effects of cannabis are not clear

[29] Concerns include memory and cognition problems, risk of addiction, schizophrenia in young people, and the risk of children taking it by accident [30].

People who have a greater risk of developing schizophrenia are more likely to try cannabis, according to new research, which also found a causal link between trying the drug and an increased risk of the condition.

But several studies confirmed the increased risk of psychosis for vulnerable people who use the drug and an increase use of particularly high potency strains of cannabis among young people.

However, experts cautioned that the risks should not be overstated given the need for greater research into links between mental health and illicit drugs. “The evidence suggested that schizophrenia risk predicts the likelihood of trying cannabis” [31]. The relationship could operate in both directions. They’re more about providing evidence that the relationship is actually causal, rather than the result of confounding or common risk factors.”

While some evidence was found to support hypotheses that cannabis use is a contributory factor in increasing the risk of schizophrenia, the researchers were surprised to find stronger evidence that the opposite was also likely. This adds weight to the idea that the drug may be used as a form of self-medication.

THC is responsible for many of the harmful effects of cannabis, such as paranoia and anxiety, whereas CBD appears to reduce these symptoms. Antipsychotic medications act by blocking dopamine receptors in the brain. However, dopamine is not the only neurotransmitter whose function is altered during psychosis. And, in some patients, dopamine function can even be relatively normal. So there is a need for new drugs that target other neurotransmitter systems that are implicated in psychosis.

Some research found that was a reduction in symptoms of schizophrenia in the patients treated with CBD, and the clinicians looking after them thought that they had got better. The rate of possible side effects in patients given CBD was no more than in patients who were given the placebo.

While it is still unclear exactly how CBD works, we know that it acts in a different way to antipsychotic medication, so it could represent a new class of treatment. The absence of side effects is also potentially important; as a key problem in caring for patients with psychosis is that they are often reluctant to take antipsychotic drugs because of concerns about side effects.

The next steps are to carry out larger trials of CBD to confirm these initial promising findings, and to assess the effectiveness of CBD in other types of patient. Several states have made it legal for CBD to be used for medical reasons.

Recent studies suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder [9].

Conclusion:

Even though most of herbalists interviewed in this study with the new researches accord that CBD could be a beneficial addition to the treatment of psychiatric disorders. It cannot be denied that cannabis has been linked for decades to the onset of psychosis, this conclusion corroborate with a lot of researches [32-33]. And the repeated use of this substance has already been associated with several health problems such as addictions, initiation and maintenance of smoking, some mental illnesses (depression, anxiety disorders and schizophrenia) [34-35]. In our next studies, we will explore these two contradictory functions of cannabis in order to satisfy our curiosity to discover how our animal models will act on behavioral tests after treatment with cannabinoids.

Abbreviations

CBC: cannabichromene

CBD: cannabidiol

CBG: cannabigerol

CBL: cannabicyclol

CBN:cannabinol

GABA: gamma aminobutyric acid

THC: tetrahydrocannabinol

TRP: transient receptor potential channels

Acknowledgements

The authors warmly thank all Moroccan herbalists for giving appropriate and valuable information about utilization of herbal as a remedy for Schizophrenia.

Funding

There was no funding

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors contributions

ZILA carried out the field surveys and data collection. ZILA and ZD processed the data and performed the statistical analyses. ZILA and ZD drafted the manuscript. KT and KA revised the manuscript critically to its present form. All authors read the final manuscript and agreed to its submission.

Competing interests

The authors declare that they have no competing interests.

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Cannabis sativa L. Melissa officinalis Lippia citriodora Crataegus monogyna Origanum majorana Valeriana officinalis Chamomilla nobilis Foeniculum vulgare Lavandula officinalis Mercurialis annua Passiflora incarnata Ammodaucus leucotrichus Citrus aurantium.L Hibiscus esculens Illicium verum Myristica Fragrans Papaver rhoeas Papaver somniferum Pimpinella anisum Rosmarinus officinalis Salvia officinalis Syzygium aromaticum Thymelaea hirsuta Tilia cordata Urtica urens Viscum album 0.25 0.25 0.2 0.15000000000000024 0.15000000000000024 0.15000000000000024 0.1 0.1 0.1 0.1 0.1 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2 5.0000000000000114E-2

Lamiaceae Cannabaceae Apiaceae Verbenaceae Rosaceae Valerianaceae Astéraceae Euphorbiaceae Papaveraceae Passifloraceae Illiciaceae Malvaceae Myrtaceae Myrtaceaeisticaceae Rutaceae Tiliaceae Thymelaeaceae Urticaceae Viscaceae 0.60000000000000064 0.25 0.2 0.2 0.15000000000000024 0.15000000000000024 0.1 0.1 0.1 0.1 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2 5.0000000000000093E-2

leaves; 50%

Flowers; 45%

Seeds; 40%

Stem;

10%

Feuille Fleure graine tige 0.5 0.45 0.4 0.1

[NOM DE CATÉGORIE]; [VALEUR]

Capsule; 63%

E.O; 50%

H.T; 45%

Tab; 18%

Infusion Gélule H.E tisane Capsule 0.63000000000000589 0.63000000000000589 0.5 0.45 0.18000000000000024

for

46%

Against

36%

Necessity for studies

18%

pour contre à étudier 0.45 0.36000000000000032 0.18000000000000024

Agadir

[POURCENTAGE]

Berrechid

[POURCENTAGE]

Casablanca

[POURCENTAGE]

Marrakech

[POURCENTAGE]

Tetouan

[POURCENTAGE]

Oujda

[POURCENTAGE]

[NOM DE CATÉGORIE]

[POURCENTAGE]

[NOM DE CATÉGORIE]

[POURCENTAGE]

agadir berrechid casa marrakech tetouan oujda Rabat Temara 4 1 5 2 2 2 1 3

[1-10]years [11-20]years [21-30]years [31-40]years [41-50]years 0.2 0.25 0.35 0.1 0.05

Primary high school BAC University Master Ph.D 0.25 0.35 0.2 0.1 0.1 0.05

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