Research

Non-Drowsy

  • Nervousness
  • Worry
  • Jittery, edgy
  • Stress
  • Fatigue
  • Muscle tension
  • Muscle aches
  • Tension headaches
  • Flashbacks
  • Anxiety attacks
  • Poor concentration
  • Feeling out of control
  • Obsessions/compulsions

KalmPro formulation ingredients (total 1500mg):

  • Inositol
  • Lavender
  • Passionflower
  • L-theanine
  • Lemon balm

Research on Supplements for Anxiety:

  • Inositol
Studies show effectiveness for: panic disorder, OCD
Side effects: nausea, fatigue, dizziness, and headache
Positive effects: few side effects

Inositol is a naturally occurring carbohydrate which is sweet in taste, and is an isomer of glucose. Inositol can be found in fruits and lechitins. Inositol is a key component of the phosphatidyl-inositol cycle, which is a second-messenger system used by serotonergic, noradrenergic, and cholinergic receptors. The reported mechanism of action of inositol is to reverse the desensitization of serotonin receptors, thereby effectively increasing the signal of the serotonin receptor downstream (Levine, 1997). This is hypothesized to have similar effect as SSRIs (selective serotonin reuptake inhibitors) to decrease the reuptake of serotonin in the synapse, thereby increasing serotonin in the synapse and increasing the signal from the serotonin receptor postsynaptically.

One study found that inositol was as effective as fluvoxamine for the treatment of panic disorder (Palatnik et al., 2001), while a different study found inositol to be more effective than placebo for panic disorder (Benjamin et al., 1995). Another study found it effective in obsessive compulsive disorder (OCD) (Fux et. al., 1996). Inositol is a natural compound with few side effects, which makes it an attractive alternative to psychotropics which have significant side effects.

  • Lavender
Studies show effectiveness for: generalized anxiety disorder, subclinical anxiety
Side effects: nausea, belching, dyspepsia, headache, changes in appetite, and constipation
Positive effects: non-sedating, non-addictive, improves anxiety related disturbed sleep

Lavender, also known as Lavandula angustifolia, is a flowering plant in the mint family, and is native to the Old World. It is hypothesized that lavender has benzodiazepine-like action, without the side effects of benzodiazepines, such as tolerance, dependence, and abuse potential (Silenieks et al., 2013).

In a study that was just published, Kasper et al. (2014) studied lavender oil, Silexan, comparing it to placebo and paroxetine in an RCT for generalized anxiety disorder, and found that lavender oil was more effective than placebo for anxiety. In addition, lavender oil had fewer side effects than paroxetine, and had a side effect profile comparable to the placebo (Kasper et al., 2014). Another study showed that lavender oil was as effective as lorazepam for generalized anxiety disorder, and does not have the sedative or addictive potential of benzodiazepines (Woelk and Schläfke, 2010). Additionally, lavender showed effectiveness for subclinical anxiety when compared to placebo, and improved anxiety related disturbed sleep without causing sedation (Kasper et al., 2010).

  • Passionflower
Studies show effectiveness for: generalized anxiety disorder, pre-surgery anxiety, insomnia
Dosage: 90mg daily
Side effects: dizziness, confusion, irregular muscle action and coordination, altered consciousness, and inflamed blood vessels
Positive effects: non-sedating, does not cause job impairment

Passiflora incarnata, commonly known as Passionflower, is a flowering plant, and has a pantropical distribution. Passiflora modulates the GABA system by binding to GABA receptors and inhibiting the reuptake of GABA (Appel et al., 2011).

One study revealed that Passionflower was as effective as oxazepam for generalized anxiety disorder, and that oxazepam caused impairment in job performance (Akhondzadeh et al., 2001). Another study showed that Passiflora reduces anxiety in surgery patients pre-operatively (Movafegh et. al., 2008). Additionally, Passiflora tea improved sleep in people with mild sleep problems when compared to placebo tea (Ngan and Conduit, 2011).

  • L-theanine
Studies show effectiveness for: non-clinical anxiety Side effects: headache, dizziness, and GI symptoms Positive effects: safe and well-tolerated

L-theanine is an amino acid found in green tea. The mechanism of action of l-theanine for its anxiolytic and calming effect is due to the up-regulation of inhibitory neurotransmitters such as GABA, and it may also modulate serotonin and dopamine neurotransmitters (Lardner, 2014).

In one study, theanine reduced anxiety symptoms more than placebo in healthy subjects (Unno et al., 2013). In another study, L-theanine augmentation of antipsychotic medications for those with psychosis was more effective than placebo augmentation for reduction of anxiety symptoms (Ritsner et al., 2011). L-theanine can also cause a relaxed state while also improving concentration (Kobayashi et al., 1998).

  • Lemon balm
Studies show effectiveness for: anxiety disorders, non-clinical anxiety, sleep disturbance, stress
Side effects: nausea, vomiting, abdominal pain, dizziness, and wheezing
Positive effects: safe

Melissa officinalis, commonly known as lemon balm, is a herb in the mint family, and native to Europe and the Mediterranean. The mechanism of action of lemon balm appears to decrease corticosteroids and increase GABA levels (Yoo et al., 2011).

One study showed that lemon balm combined with Valerian led to anxiolytic effects in healthy subjects when compared to placebo (Kennedy et al., 2006), and another study showed it reduced stress in healthy volunteers (Kennedy et al., 2004). Additionally, a study showed effectiveness for mild to moderate anxiety disorders and sleep disturbances (Cases et al., 2011).

Questions:

  • What are the ingredients in KalmPro designed to do for you?
    The ingredients in KalmPro can help for the following symptoms: nervousness, worry, jittery, edgy, stress, fatigue, muscle tension, muscle aches, tension headaches, flashbacks, nightmares, anxiety attacks, poor concentration, feeling out of control, and obsessions/compulsions.
  • Where do other supplements and prescription drugs fail?
    Although prescription drugs are effective for anxiety, many people discontinue prescription drugs because of side effects. In addition, prescription drugs tend to be expensive, especially when the drug is still on patent, and no cheaper generic drug is available. Increasingly, insurance companies are reimbursing less and less of these prescription drugs, leaving the patient to bear the burden of the huge expense of prescription medications. While natural supplements are general safe, not all of them have a benign side effect profile (e.g. kava use has a risk of serious liver problems). And many natural supplements do not have research studies showing effectiveness in anxiety. KalmPro is different, as it combines safe and effective natural supplements that are backed by research studies.
  • What parts of the brain is KalmPro supposed to effect?
    The natural supplement ingredients in KalmPro target similar parts of the brain that the prescription drugs target. For example, the ingredients in KalmPro target the part of the brain called the amygdala, part of the fear circuit, and it modulates fear and anxiety. KalmPro also targets the cortico-striatal-thalamic-cortical circuit in the brain, also known as the worry circuit, and it modulates worry, ruminating negative thoughts, anticipatory anxiety, and obsessions.
  • How exactly do the ingredients in KalmPro work?

    • Inositol reverses the desensitization of serotonin receptors, thereby effectively increasing the signal of the serotonin receptor downstream, similar to SSRI’s effect on increasing serotonin

    • Lavender works similarly to benzodiazepines, enhancing GABA, without the dependence and abuse potential of benzodiazepines

    • Passiflora modulates the GABA system by binding to GABA receptors and inhibiting the reuptake of GABA, so it modulates GABA like benzodiazepines, without the side effects of benzodiazepines

    • L-theanine up-regulates inhibitory neurotransmitters such as GABA, and it may also modulate serotonin and dopamine neurotransmitters, so it has a dual action, similar to having benzodiazepine- and SSRI- like actions

    • Lemon balm appears to decrease corticosteroids (like cortisol) and increase GABA levels, so it may decrease stress hormones and modulate GABA, similar to benzodiazepines, but without the side effects

References:

Controlled trials of inositol in psychiatry.
Levine J.
Eur Neuropsychopharmacol. 1997 May;7(2):147-55.
Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder.
Palatnik A, Frolov K, Fux M, Benjamin J.
J Clin Psychopharmacol. 2001 Jun;21(3):335-9.
Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder.
Benjamin J, Levine J, Fux M, Aviv A, Levy D, Belmaker RH.
Am J Psychiatry. 1995 Jul;152(7):1084-6.
Inositol treatment of obsessive-compulsive disorder.
Fux M, Levine J, Aviv A, Belmaker RH.
Am J Psychiatry. 1996 Sep;153(9):1219-21.
Silexan, an essential oil from flowers of Lavandula angustifolia, is not recognized as benzodiazepine-like in rats trained to discriminate a diazepam cue.
Silenieks LB, Koch E, Higgins GA.
Phytomedicine. 2013 Jan 15;20(2):172-7.
Lavender oil preparation Silexan is effective in generalized anxiety disorder - a randomized, double-blind comparison to placebo and paroxetine.
Kasper S, Gastpar M, Müller WE, Volz HP, Möller HJ, Schläfke S, Dienel A.
Int J Neuropsychopharmacol. 2014 Jun;17(6):859-69.
A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder.
Woelk H, Schläfke S.
Phytomedicine. 2010 Feb;17(2):94-9.
Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial.
Kasper S, Gastpar M, Müller WE, Volz HP, Möller HJ, Dienel A, Schläfke S.
Int Clin Psychopharmacol. 2010 Sep;25(5):277-87.
Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L.
Appel K, Rose T, Fiebich B, Kammler T, Hoffmann C, Weiss G.
Phytother Res. 2011 Jun;25(6):838-43.
Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam.
Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M.
J Clin Pharm Ther. 2001 Oct;26(5):363-7.
Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study.
Movafegh A, Alizadeh R, Hajimohamadi F, Esfehani F, Nejatfar M.
Anesth Analg. 2008 Jun;106(6):1728-32.
A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality.
Ngan A, Conduit R.
Phytother Res. 2011 Aug;25(8):1153-9.
Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders.
Lardner AL.
Nutr Neurosci. 2014 Jul;17(4):145-55.
Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary α-amylase activity, trait anxiety and subjective stress.
Unno K, Tanida N, Ishii N, Yamamoto H, Iguchi K, Hoshino M, Takeda A, Ozawa H, Ohkubo T, Juneja LR, Yamada H.
Pharmacol Biochem Behav. 2013 Oct;111:128-35.
L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study.
Ritsner MS, Miodownik C, Ratner Y, Shleifer T, Mar M, Pintov L, Lerner V.
J Clin Psychiatry. 2011 Jan;72(1):34-42.
K. Kobayashi et al., “Effects of L Theanine on the Release of Alpha-Brain Waves in Human Volunteers,” Journal of the Agricultural Chemical Society of Japan 72, no. 2 (1998): 153–157.
Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus.
Yoo DY, Choi JH, Kim W, Yoo KY, Lee CH, Yoon YS, Won MH, Hwang IK.
Neurochem Res. 2011 Feb;36(2):250-7.
Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress.
Kennedy DO, Little W, Haskell CF, Scholey AB.
Phytother Res. 2006 Feb;20(2):96-102.
Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Kennedy DO, Little W, Scholey AB.
Psychosom Med. 2004 Jul-Aug;66(4):607-13.
Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances
Julien Cases, Alvin Ibarra, Nicolas Feuillère, Marc Roller, Samir G. Sukkar
Med J Nutrition Metab. 2011 December; 4(3): 211–218