The components of loss before income taxes for the years ended December 31, 2020, 2019, and 2018, are presented below:



	2020		2019		2018
Domestic	$	(15,768,224)	$	(12,950,725)	$	(9,702,869)
Foreign		(631,761)		(276,917)		(679,190)
Loss before income taxes	$	(16,399,985)	$	(13,227,642)	$	(10,382,059)

Income taxes computed using the federal statutory income tax rate differs from the Company’s effective tax rate for the years ended December 31, 2020, 2019, and 2018, primarily due to the following:



	2020		2019		2018
Income tax benefit	$	(3,443,997)	$	(2,777,805)	$	(2,180,233)
State and provincial income tax, net of federal benefit		(732,994)		397,081		(534,789)
Permanent differences		131,141		219,549		53,795
US-Foreign rate differential		(142,663)		38,776		(13,955)
Other, net		(145,973)		866,250		1,182,900
	$	(4,334,486)	$	(1,256,149)	$	(1,492,282)
Change in valuation allowance		4,334,486		1,256,149		1,492,282
Total income tax	$	—	$	—	$	—

As of December 31, 2020, the Company has domestic net operating loss carryforwards of approximately $56 million, after consideration of limitations pursuant to section 382, to offset future federal taxable income, which begin to expire in 2031. At December 31, 2020, the Company has domestic net operating loss carryforwards of approximately $27 million, which can be carried forward indefinitely. The future utilization of certain historic net operating loss and tax credit carryforwards, however, is subject to annual use limitations based on the change in stock ownership rules of Internal Revenue Code Sections 382 and 383. The Company experienced a change in ownership under these rules during 2012 and revised its calculation of net operating loss carryforwards based on annual limitation rules. The Company also has foreign research loss carryforwards totaling approximately $10.0 million and foreign research and development expense tax credits of approximately $2.7 million at December 31, 2020, which expire at various times commencing in 2021. Since the Company has incurred only losses from inception and there is uncertainty related to the ultimate use of the loss carryforwards and tax credits, a valuation allowance has been recognized to offset the Company’s deferred tax assets, and no benefit for income taxes has been recorded.

Significant components of the Company’s deferred tax assets and liabilities are as follows:



		2020		2019
Deferred tax assets:
Net operating loss carryforwards	$	16,964,199	$	12,251,892
Foreign research and development tax credit carryforwards		2,679,180		2,564,679
Property and equipment		56,697		429,764
Intangibles		3,122,394		3,241,649
Total deferred tax assets	$	22,822,470	$	18,487,984
Valuation allowance	$	(22,822,470)	$	(18,487,984)
Net deferred tax assets	$	—	$	—