**Abstract**

Substantial number of studies has been conducted to find alternatives or treatments for psychosis. Psychosis represents a variety of mental disorders characterized by the presence of delusions, hallucinations and grossly disorganized thinking in a clear sensorium. Psychosis is burdensome and difficult to treat given the inability of the typical and atypical antipsychotics to adequately manage it, accompanied by numerous disturbing adverse effects. Therefore, many with chronic mental health problems justifiably feel disappointed by the apparent ineffectiveness of conventional treatment and naturally search for a more holistic approach to treatment and alternative medicines having less or no side-effects. Plants are rich in secondary metabolites which have the ability to interact with the Central nervous system (CNS) to produce effects that can be beneficial for the management of psychosis, these phytochemicals are believed to have minimal adverse effects. A review of some of the medicinal plants used as antipsychotics, indicated that many medicinal plants possess antipsychotic effects that can improve the treatment of psychosis. Apparently, further studies are necessary in order to isolate the active constituents, ascertain their molecular mechanisms and safety, and also to test them in clinical studies for the development of new pharmacotherapies for psychosis.

**Keywords:** Medicinal plants, Molecular mechanisms, Psychosis, Secondary metabolites, Antipsychotics

### **1. Introduction**

The term "psychosis" denotes a variety of mental disorders: the presence of delusions, various types of hallucinations, usually auditory or visual, but sometimes tactile or olfactory, and grossly disorganized thinking in a clear sensorium. Schizophrenia is an enduring, disabling psychiatric illness affecting about 1% of the population globally. It is characterized by various symptoms classified into positive, negative and cognitive) [1, 2].

Plants provide the essential nutrients and remedy needed by humans, they are healthier compared to animal diets. Over time much benefits have been derived from medicinal plants due to their rich natural phytochemicals that interact favorably with the human body and neurotransmitters to produce effects that are beneficial to man. In this chapter we will look at some medicinal plant used in the pharmacotherapy of psychosis.

## **2. Management of psychosis**

Psychosis is an immense social and economic problem, but the management of psychosis remains insufficient. Basically typical and atypical antipsychotics are used for the treatment of schizophrenia, the typical antipsychotics such as chlorpromazine and haloperidol are only effective in the treatment of positive symptoms, and are accompanied by disturbing adverse effects such as extrapyramidal side-effects [3], the atypical antipsychotic drugs such as risperidone and olanzapine provide some beneficial effects on negative symptoms and cognitive deficits [4], but they are inadequate and mild. Prolonged use also results in increased oxidative load [5] which could lead to cardiovascular disorders, diabetes, and agranulocytosis seen with clozapine, they also cause moderate to severe weight gain [2, 6–8]. The use of medicinal plants as complementary remedies for the treatment of psychosis have become necessary because of their characteristically high chemical diversity, biochemical specificity, and several other properties that make them favorable lead structures for the treatment of various disorders, including psychosis [9], for example, *Alpinia zerumbet* (Pers.) B. L. Burtt (Zingiberaceae) [10], *Lonchocarpus cyanescens* (Schumach and Thonn.) Benth. (Fabaceae) [11] etc., which have been used in the pharmacotherapy of psychosis. Interestingly many of these plants were studied and found to have lesser side effects e.g. catalepsy [12–15] indicating that these plants may not cause extrapyramidal side effects in humans.

Medicinal plants are either used as an alternative or in addition to orthodox medicine [16], users search for a more holistic approach to treatment, others expect that alternative medicines have less or no side-effects, and many with chronic mental health problems justifiably feel disappointed by the apparent ineffectiveness of conventional treatment [17].

#### **3. Review of relevant pathophysiology**

Neuropsychiatric Disorders may occur as a result of a number of factors such as genetic predisposition, lifestyle factors such as substance abuse and recently diet is also believed to be a factor [18] due to certain observations that associated incidence of psychotic episodes in neuropsychiatric diseases with poor dietary patterns, such as a lower intake of omega-3 fatty acids, vegetables, fibers, fruits, vitamins and minerals [19], all these are substances that can be obtained naturally supporting the use of natural products in psychosis especially because of the high antioxidant content of these natural products, since oxidative stress is implicated in psychosis.

## **4. Secondary metabolites in medicinal plants for psychosis**

The discovery of effective plant-based medicinal plants for the treatment of psychosis is constrained by a need to conclusively identify relevant active constituents and understand synergies within them and an inability to sufficiently standardize replicable extracts.

A large number of natural phytochemicals are claimed to have beneficial effects on the adequate functioning of the human brain [20]. Essentially, metabolites produce effects on human brain function probably due to the connection between plant, mammalian biochemistry and molecular functioning. Principally, as a result of the numerous molecular signaling pathways that are conserved between taxa and their role in the synthesis of secondary metabolite [21]. Secondly the effects might

#### *Medicinal Plants Used in the Management of Psychosis DOI: http://dx.doi.org/10.5772/intechopen.100224*

be based on the similarities between the prevalent natural herbivores of plants and the nervous systems of humans. Therefore, the phytochemicals whose synthesis has been retained by a process of natural selection and on the basis of their ability to interact with the CNS of herbivorous or symbiotic insects will also interact with the human CNS system via the same mechanisms [22]. Some of the significance of secondary metabolites involve general protective roles (such as antioxidant, ultra violet (UV) light-absorbing, free radical-scavenging and antiproliferative agents) and preservation the plant against microorganisms such as bacteria, fungi, and viruses. More intricate actions involve dictating or modifying the plant's relationship with more complex organisms [23–25]. This is achieved primarily by their role of feeding deterrence, consequently, many phytochemicals are bitter and/or toxic to potential herbivores, with this toxicity often extending to direct interactions with the herbivore's central and peripheral nervous systems [26] identified extracts and constituents from 85 individual medicinal plants that have potential efficacy for treating psychiatric disorder. Accordingly, secondary metabolites often act as agonists or antagonists of neurotransmitter systems [25, 27] or form structural analogs of endogenous hormones [28].

Secondary metabolites can be subdivided into many distinct groups base on their chemical structure and synthetic pathways, furthermore, these groups can be broadly categorized in terms of the nature of their ecological roles and also their eventual effects and comparative toxicity in the consuming animal. The phytochemicals are herewith, discussed base on the chemical nature of their alleged active components. The largest and most widespread of phytochemical groups are the alkaloids, phenolic compounds and terpenes.

### **4.1 Alkaloids**

Alkaloids are a structurally diverse group of over 12,000 cyclic nitrogencontaining compounds that are found in over 20% of plant species [29]. The use of alkaloids for medicinal purposes dates as far back as the Stone Age [20].

The alkaloids are known to be the common poisons, neurotoxins, and traditional psychedelics for example atropine, scopolamine, and hyoscyamine, from *Atropa Belladonna* plant and social drugs such as ephedrine, nicotine, opiates, cocaine, and caffeine widely consumed for recreational purposes [30]. Despite their posoinous nature, this group of chemicals also found application in the treatment of Alzheimer's Disease, because of their cholinesterase inhibiting effects e.g. riverstigmine, huperzine, physostigmine, and huperzine [31].

Gentianine is a major alkaloid extracted from *Swertia chirata* Linn (Gentianaceae), it was reported to possess antipsychotic activity in experimental animals by antagonizing amphetamine induced stereotypy [32]. 11-demethoxyreserpiline, 10- demethoxyreserpiline, α-yohimbine and reserpiline are alkaloids isolated from the leaves of *Rauwolfia tetraphylla* and are found to possess atypical antipsychotic-like actions [33]. alstonine an indole alkaloid isolated from *Picralima nitida* Alstonine was found to possess antipsychotic properties [34, 35].

#### **4.2 Phenolic compounds**

Phenolic compounds are universally found across the plant kingdom, with approximately 10,000 structures identified to date. Phenolics are synthesized from precursors produced by the phenylpropanoid pathway with the exception of a few notable compounds. Structurally, they share at least one aromatic hydrocarbon ring with one or more hydroxyl groups attached [22].

Phenolic compounds comprise of simple low-molecular weight compounds, such as the coumarins, simple phenylpropanoids, and benzoic acid derivatives, to more complex structures such as flavanoids, tannins and stilbenes [22]. These compounds play an important role in CNS functioning by interacting directly with neurotransmitter systems. In in vivo models, phenolics enhance cognition through antagonistic gamma-aminobutyric acid (GABA) receptor binding, with resultant cholinergic upregulation and exert antidepressant effects via monoamine oxidase inhibition in the brain, sedative, anxiolytic and antipsychotic effects by binding to GABA receptors, [36–38]. Flavonoids are widely distributed throughout the plant kingdom. They are constituents of medicinal plants used as herbal medicines in traditional medical practice, and are now considered valuable therapeutic agents in modern medicines [39, 40]. Many studies have reported that flavones modulate neurotransmission through enhancement of GABA activity in the central nervous system; which led to the hypothesis that they could exert tranquilizing effects in behavioral hyperactivity such as schizophrenia [41, 42]. Undeniably, a number of evidences have implicated the role of altered GABAergic transmission in the pathophysiology of schizophrenia [43, 44]. Morin a flavonoid isolated from plants was found to exhibit antipsychotic effects [45].

#### *4.2.1 Tannins*

Tannins are a group of plant secondary metabolites that have the ability to tan or convert animal skin into leather. These compounds are classified as being water soluble phenolics with the ability to precipitate alkaloids, gelatins, and other proteins. High tannin concentrations are found in nearly every part of many plants, such as in the bark, wood, leaves, fruit, roots, plant galls, and seed. Tannins may exert their biological effects in two different ways: as unabsorbables, these are usually complex structures with binding properties which may produce local effects in the gastrointestinal tract (antioxidant, radical scavenging, antimicrobial, antiviral, antimutagenic, and antinutrient effects), or as absorbable, these are usually low molecular weight structures which are easily absorbed, and produce systemic effects in various organs [46]. Gallic acid, a gallotanin found in many plants was reported to demonstrate anti-schizophrenic activity primarily due to its antioxidant and anti-inflammatory effects [47]. A novel tannin composition effective in treating mental diseases such as acute or chronic schizophrenia, was isolated from Rhubarb (Rhe; Rhi zoma) a kind of crude drug known from the past and has been frequently used as a Japanese-Chinese medicine [48].

#### *4.2.2 Saponins*

Saponins are naturally occurring, but functionally and structurally diverse phytochemicals that are broadly distributed in plants. They are a complex and chemically varied group of compounds consisting of triterpenoid or steroidal glycones linked to oligosaccharide moieties. Although there is a scarce documentation on the antipsychotic potential of saponin, polygalasaponins, a saponin isolated from *Polygalae tenuifolia* was reported to possessed antipsychotic effects [49].

#### **4.3 Terpenes**

Terpenes are a diverse group of more than 30,000 lipid-soluble compounds. Their structure includes 1 or more 5-carbon isoprene units, Terpenoids are classified base on the number of isoprene units they contain; isoprene, which itself is synthesized and released by plants, comprises 1 unit and is classified as a hemiterpene;

monoterpenes incorporate 2 isoprene units, sesquiterpenes incorporate 3 units, diterpenes comprise 4 units, sesterpenes include 5 units, triterpenes incorporate 6 units, and tetraterpenes 8 units [22]. Some of the recognized antipsychotic terpenoids are myrcene, beta-caryophyllene and limonene. However, these terpenoids do not only have antipsychotic properties but possess anti-depressant effects due to the suppression and activation of the cannabinoid receptor 2 [20].
